Mast cells and eosinophils in invasive breast carcinoma

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Amini, Rose-Marie; Aaltonen, Kirsimari; Nevanlinna, Heli; Carvalho, Ricardo; Salonen, Laura; Heikkilä, Päivi; Blomqvist, Carl

2007-01-01

Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas. Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome. Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours. A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers

The role of the eosinophil-selective chemokine, eotaxin, in allergic and non-allergic airways inflammation

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Conroy Dolores M

1997-01-01

Full Text Available Blood eosinophilia and tissue infiltration by eosinophils are frequently observed in allergic inflammation and parasitic infections. This selective accumulation of eosinophils suggested the existence of endogenous eosinophil-selective chemoattractants. We have recently discovered a novel eosinophil-selective chemoattractant which we called eotaxin in an animal model of allergic airways disease. Eotaxin is generated in both allergic and non-allergic bronchopulmonary inflammation. The early increase in eotaxin paralled eosinophil infiltration in the lung tissue in both models. An antibody to IL-5 suppressed lung eosinophilia, correlating with an inhibition of eosinophil release from bone marrow, without affecting eotaxin generation. This suggests that endogenous IL-5 is important for eosinophil migration but does not appear to be a stimulus for eotaxin production. Constitutive levels of eotaxin observed in guinea-pig lung may be responsible for the basal lung eosinophilia observed in this species. Allergen-induced eotaxin was present mainly in the epithelium and alveolar macrophages, as detected by immunostaining. In contrast there was no upregulation of eotaxin by the epithelial cells following the injection of Sephadex beads and the alveolar macrophage and mononuclear cells surrounding the granuloma were the predominant positive staining cells. Eotaxin and related chemokines acting through the CCR3 receptor may play a major role in eosinophil recruitment in allergic inflammation and parasitic diseases and thus offer an attractive target for therapeutic intervention.

Eosinophilic esophageal myositis diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: a case report.

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Igarashi, Ryo; Irisawa, Atsushi; Shibukawa, Goro; Yamabe, Akane; Fujisawa, Mariko; Sato, Ai; Maki, Takumi; Arakawa, Noriyuki; Yoshida, Yoshitsugu; Yamamoto, Shogo; Ikeda, Tsunehiko

2016-10-01

Eosinophilic esophagitis (EoE) is diagnosed by microscopic findings of eosinophilic infiltration into the squamous epithelium. In contrast, another disease concept termed "eosinophilic esophageal myositis (EoEM)" has been proposed, whereby there is eosinophilic infiltration into the muscularis propria instead. A 60-year-old man was referred to our hospital for chest pain, dysphagia, and several episodes of esophageal food impaction. Although EoE was suspected based on clinical features, biopsy specimens showed no mucosal eosinophilic infiltration. Endoscopic ultrasound (EUS) showed thickening of the muscularis propria layer and subsequent EUS-guided fine-needle aspiration biopsy (EUS-FNA) revealed eosinophilic infiltration into the muscularis propria. Although the patient's symptoms gradually improved after steroid administration, complete remission was not achieved after 1 year of treatment. This case may reflect a disorder distinct from typical EoE based on eosinophilic infiltration of the muscularis propria but not the squamous epithelium, and we, therefore, diagnosed it as EoEM using the EUS-FNA findings as reference.

Eosinophils as a novel cell source of prostaglandin D2: autocrine role in allergic inflammation

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Luna-Gomes, Tatiana; Magalhães, Kelly G; Mesquita-Santos, Fabio P.; Bakker-Abreu, Ilka; Samico, Rafaela F.; Molinaro, Raphael; Calheiros, Andrea S.; Diaz, Bruno L.; Bozza, Patrícia T.

2011-01-01

Prostaglandin (PG)D2 is a key mediator of allergic inflammatory diseases that is mainly synthesized by mast cells, which constitutively express high levels of the terminal enzyme involved in PGD2 synthesis, the hematopoietic PGD synthase (H-PGDS). Here, we investigated whether eosinophils are also able to synthesize, and therefore, supply biologically active PGD2. PGD2 synthesis was evaluated within human blood eosinophils, in vitro-differentiated mouse eosinophils, and eosinophils infiltrating inflammatory site of mouse allergic reaction. Biological function of eosinophil-derived PGD2 was studied by employing inhibitors of synthesis and activity. Constitutive expression of H-PGDS was found within non-stimulated human circulating eosinophils. Acute stimulation of human eosinophils with A23187 (0.1 – 5 μM) evoked PGD2 synthesis, which was located at the nuclear envelope and was inhibited by pre-treatment with HQL-79 (10 μM), a specific H-PGDS inhibitor. Pre-stimulation of human eosinophils with arachidonic acid (AA; 10 μM) or human eotaxin (6 nM) also enhanced HQL-79-sensitive PGD2 synthesis, which, by acting on membrane-expressed specific receptors (DP1 and DP2), displayed an autocrine/paracrine ability to trigger leukotriene (LT)C4 synthesis and lipid body biogenesis, hallmark events of eosinophil activation. In vitro-differentiated mouse eosinophils also synthesized paracrine/autocrine active PGD2 in response to AA stimulation. In vivo, at late time point of the allergic reaction, infiltrating eosinophils found at the inflammatory site appeared as an auxiliary PGD2-synthesizing cell population. Our findings reveal that eosinophils are indeed able to synthesize and secrete PGD2, hence representing during allergic inflammation an extra cell source of PGD2, which functions as an autocrine signal for eosinophil activation. PMID:22102725

Eosinophilic ascites: A case report and literature review

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Raed M Alsulaiman

2015-01-01

Full Text Available Eosinophilic gastroenteritis is a rare gastrointestinal (GI disorder characterized by nonspecific GI symptoms, peripheral eosinophilia, and eosinophilic infiltration of the intestinal wall. The disorder is classified into mucosal, muscular, and sub-serosal types, depending on the clinical picture and the depth of eosinophilic infiltration within the GI wall. Sub-serosal disease, which is complicated by ascites, usually results in the most severe clinical form of eosinophilic gastroenteritis and requires early corticosteroid therapy. In such cases, a favorable outcome can be achieved after a short course of corticosteroids. We present the case of a 28-year-old female with diffuse abdominal pain and distention for 2 weeks. Her physical examination was significant for moderate ascites. Initial work-up demonstrated severe peripheral blood eosinophilia, normal liver function tests, and elevated serum immunoglobulin E (IgE. Upper endoscopy, colonoscopy showed a thickening of the stomach and colon, and biopsies showed marked eosinophilic infiltration of the mucosa. Ascitic fluid analysis showed significant eosinophilia. Subsequent treatment with oral prednisone resulted in the normalization of laboratory and radiologic abnormalities 45 days after the start of the treatment. Despite its rarity, eosinophilic gastroenteritis needs to be recognized by the clinician because the disease is treatable, and timely diagnosis and initiation of treatment could be of major importance.

Eosinophilic Otitis Media: the Aftermath of Eosinophil Extracellular Trap Cell Death.

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Ueki, Shigeharu; Ohta, Nobuo; Takeda, Masahide; Konno, Yasunori; Hirokawa, Makoto

2017-05-01

Eosinophilic otitis media (EOM) is a refractory disease characterized by the accumulation of eosinophils in middle ear effusion and mucosa. We summarize current knowledge regarding the clinical characteristics and management of EOM. Although eosinophil activation in inflamed foci is involved in the pathogenesis of EOM, little is known about the fate of the eosinophils and aftermath of their cell death. We discuss the possibility that eosinophils undergo non-apoptotic cell death that worsens tissue damage and increases effusion viscosity. Unlike chronic otitis media, EOM is strongly associated with an allergic background. Corticosteroids are currently the only effective pharmacological treatment, and surgical intervention is often required. Mucosal eosinophils infiltrate extensively into the middle ear cavity where they are stimulated by locally produced activators including interleukin-5 and eotaxin. The eosinophils undergo cytolysis in the effusion, which represents a major fate of activated eosinophils in vivo. Recent data revealed cytolysis could be renamed as extracellular trap cell death (ETosis). ETosis represents suicidal cell death involving total cell degranulation and development of sticky chromatin structures (extracellular traps (ETs)). The characteristics of eosinophil- and neutrophil-derived ET polymers might contribute to the difference in viscosity of secretions between EOM and common chronic otitis media. The extracellular products remaining after eosinophil ETosis are an important aspect of EOM pathology. The concept of ETosis also has novel implications for potential therapeutic modalities in various eosinophilic disorders.

An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock.

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Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P

2015-01-01

Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration.

Chronic eosinophilic pneumonia presenting with ipsilateral pleural effusion: a case report.

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Sriratanaviriyakul, Narin; La, Hanh H; Albertson, Timothy E

2016-08-12

Chronic eosinophilic pneumonia is a rare idiopathic interstitial lung disease. The nearly pathognomonic radiographic finding is the peripheral distribution of alveolar opacities. Pleural effusions are rarely seen. We report a case of chronic eosinophilic pneumonia with transudative eosinophilic pleural effusion. A 57-year-old Hispanic woman, a nonsmoker with a history of controlled asthma, presented to the hospital with unresolving pneumonia despite three rounds of antibiotics over a 2-month period. She was later diagnosed with chronic eosinophilic pneumonia based on the presence of peripheral blood eosinophilia, the peripheral distribution of alveolar infiltrates on chest radiograph, and a lung parenchymal biopsy with infiltrates of eosinophils. Upon presentation, our patient had a right-sided moderate-sized pleural effusion. The pleural fluid profile was consistent with a transudative effusion with eosinophil predominance. Our patient responded promptly to oral corticosteroid treatment in a few days. The pulmonary infiltrates and pleural effusion subsided on a 1-month follow-up chest radiograph after starting corticosteroid treatment. We report the first case of chronic eosinophilic pneumonia presenting with pneumonia with ipsilateral transudative eosinophilic pleural effusion. Like other cases of chronic eosinophilic pneumonia, early recognition and diagnosis is essential and prompt treatment with corticosteroids is the mainstay of therapy. Pleural effusion resolved without the further need for therapeutic thoracentesis.

Differentiation of eosinophilic leukemia EoL-1 cells into eosinophils induced by histone deacetylase inhibitors.

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Ishihara, Kenji; Takahashi, Aki; Kaneko, Motoko; Sugeno, Hiroki; Hirasawa, Noriyasu; Hong, JangJa; Zee, OkPyo; Ohuchi, Kazuo

2007-03-06

EoL-1 cells differentiate into eosinophils in the presence of n-butyrate, but the mechanism has remained to be elucidated. Because n-butyrate can inhibit histone deacetylases, we hypothesized that the inhibition of histone deacetylases induces the differentiation of EoL-1 cells into eosinophils. In this study, using n-butyrate and two other histone deacetylase inhibitors, apicidin and trichostatin A, we have analyzed the relationship between the inhibition of histone deacetylases and the differentiation into eosinophils in EoL-1 cells. It was demonstrated that apicidin and n-butyrate induced a continuous acetylation of histones H4 and H3, inhibited the proliferation of EoL-1 cells without attenuating the level of FIP1L1-PDGFRA mRNA, and induced the expression of markers for mature eosinophils such as integrin beta7, CCR1, and CCR3 on EoL-1 cells, while trichostatin A evoked a transient acetylation of histones and induced no differentiation into eosinophils. These findings suggest that the continuous inhibition of histone deacetylases in EoL-1 cells induces the differentiation into mature eosinophils.

Fibronectin changes in eosinophilic meningitis with blood-CSF barrier disruption.

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Shyu, Ling-Yuh; Hu, Ming-E; Chou, Chun-Hui; Chen, Ke-Min; Chiu, Ping-Sung; Lai, Shih-Chan

2015-01-01

Fibronectin, which is present at relatively low levels in healthy central nervous systems (CNS), shows increased levels in meningitis. In this study, fibronectin processing was correlated with the increased permeability of the blood-cerebrospinal fluid (CSF) barrier as well as with the formation of eosinophil infiltrates in angiostrongyliasis meningitis. The immunohistochemistry results show matrix metalloproteinase-9 (MMP-9) is localized in the choroid plexus epithelium. Coimmunoprecipitation demonstrated fibronectin strongly binds MMP-9. Furthermore, treatment with the MMP-9 inhibitor GM6001 significantly inhibited fibronectin processing, reduced the blood-CSF barrier permeability, and decreased the eosinophil counts. The decreased fibronectin processing in CSF implies decreased cellular invasion of the subarachnoid space across the blood-CSF barrier. Therefore, increased fibronectin processing may be associated with barrier disruption and participate in the extravasation and migration of eosinophils into the CNS during experimental parasitic infection. Copyright © 2015 Elsevier Inc. All rights reserved.

An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock

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Miguel Martillo

2015-05-01

Full Text Available Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration.

Radiographic and pathologic observations of eosinophilic gastroenteritis

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Jung, Lae Won [Busan Nationa University College of Medicine, Busan (Korea, Republic of); Hong, Sook Hee; Lee, Jung Dal [Busan Gospel Hospital, Busan (Korea, Republic of)

1974-10-15

This report presents two cases with eosinophilic gastroenteritis in detail. The radiographic and pathologic features of eosinophilic gastroenteritis are summarized with emphasis on the differential diagnostic features. Radiographic eosinophilic gastritis should be differentiated from gastric carcinoma and lymphoma, and eosinophilic enteritis from intestinal tuberculosis and intussusception of the small bowel in Korea where these entities are prevent. Eosinophilic gastroenteritis is pathologically characterized by diffuse infiltration of the submucosa and muscle coats with eosinophilic in conjunction with hypertrophy of individual muscle fibers. This leads to thickening of the gastrointestinal wall resulting in narrowing and obstruction of the lumen. Eosinophilic venulitis is another characteristic feature which is helpful for differentiation this entity from a parasitic infection.

Radiographic and pathologic observations of eosinophilic gastroenteritis

International Nuclear Information System (INIS)

Jung, Lae Won; Hong, Sook Hee; Lee, Jung Dal

1974-01-01

This report presents two cases with eosinophilic gastroenteritis in detail. The radiographic and pathologic features of eosinophilic gastroenteritis are summarized with emphasis on the differential diagnostic features. Radiographic eosinophilic gastritis should be differentiated from gastric carcinoma and lymphoma, and eosinophilic enteritis from intestinal tuberculosis and intussusception of the small bowel in Korea where these entities are prevent. Eosinophilic gastroenteritis is pathologically characterized by diffuse infiltration of the submucosa and muscle coats with eosinophilic in conjunction with hypertrophy of individual muscle fibers. This leads to thickening of the gastrointestinal wall resulting in narrowing and obstruction of the lumen. Eosinophilic venulitis is another characteristic feature which is helpful for differentiation this entity from a parasitic infection

Eosinophilic leukocytoclastic vasculitis - a spectrum ranging from Wells' syndrome to Churg-Strauss syndrome?

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Ratzinger, Gudrun; Zankl, Julia; Eisendle, Klaus; Zelger, Bernhard

2014-01-01

Wells' syndrome is defined as an inflammatory disorder with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Eosinophilic leukocytoclastic vasculitis shows eosinophilic infiltrates in combination with vasculitic changes. And Churg Strauss Syndrome comprises all three characteristics - eosinophilic infiltrates, vasculitis and flame figures. To determine whether these three diseases are distinct entities or different manifestations of a similar clinicopathologic process. Histopathological samples and clinical courses of 17 patients with eosinophilic infiltrates, flame figures and clinical features of Wells' syndrome were re-evaluated. Histopathologically, we focused on the presence or absence of vasculitic features. Clinically, we included only patients who were diagnosed with Wells' syndrome at least once in the course of their disease. 4 patients were finally diagnosed with Wells' syndrome, 5 with eosinophilic leukocytoclastic vasculitis and 6 with Churg Strauss syndrome. Further, we had one case of an overlap between Wells' syndrome and eosinophilic vasculitis and one case of Wegener granulomatosis. Vasculitic features were found in the samples of all patients. Histologically, we find vasculitic features in typical presentations of Wells' syndrome. Clinically, we find typical features of Wells' syndrome in patients finally diagnosed with eosinophilic leukocytoclastic vasculitis or Churg Strauss syndrome. Furthermore, we have observed and formerly reported 3 patients with progression from Wells' syndrome to Churg Strauss syndrome. Thus, we assume that eosinophilic leukocytoclastic vasculitis might form a bridge between Wells' syndrome and Churg Strauss syndrome.

Churg-Strauss syndrome with coexistence of eosinophilic vasculitis, granulomatous phlebitis and granulomatous dermatitis in bullous pemphigoid-like blisters.

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Ishibashi, Masafumi; Kudo, Saori; Yamamoto, Kyoko; Shimai, Nobuko; Chen, Ko-Ron

2011-03-01

The main histopathological features in the cutaneous lesions of Churg-Strauss syndrome (CSS) are dermal leukocytoclastic vasculitis with a variable eosinophilic infiltrate and non-vasculitic tissue eosinophilia with granuloma formation. This wide histopathological spectrum may account for the various skin manifestations of CSS. However, the unique histopathological combination of dermal eosinophilic vasculitis and subcutaneous granulomatous phlebitis accompanied by bulla formation has not been previously described. We report an unusual CSS case showing dermal necrotizing eosinophilic vasculitis and granulomatous phlebitis in purpuric lesions coupled with subepidermal blistering. The blisters showed dermal granulomatous dermatitis and eosinophilia without evidence of vasculitis. Dermal necrotizing eosinophilic vasculitis was characterized by fibrinoid alteration of the vessel wall, a prominent perivascular eosinophilic infiltrate, a few infiltrating histiocytes along the affected vessel wall, and the absence of neutrophilic infiltration. The underlying subcutaneous granulomatous phlebitis was characterized by an angiocentric histiocytic infiltrate surrounded by marked eosinophilic infiltrate. Deposition of cytotoxic proteins and radicals derived from eosinophils in the vessel walls and papillary dermis followed by a secondary granulomatous response may account for the unique clinical and histopathological features in this case. Copyright © 2010 John Wiley & Sons A/S.

GWAS identifies four novel eosinophilic esophagitis loci

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Sleiman, Patrick M. A.; Wang, Mei-Lun; Cianferoni, Antonella; Aceves, Seema; Gonsalves, Nirmala; Nadeau, Kari; Bredenoord, Albert J.; Furuta, Glenn T.; Spergel, Jonathan M.; Hakonarson, Hakon

2014-01-01

Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the oesophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which

Mapracorat, a selective glucocorticoid receptor agonist, causes apoptosis of eosinophils infiltrating the conjunctiva in late-phase experimental ocular allergy

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Baiula M

2014-06-01

Full Text Available Monica Baiula,1 Andrea Bedini,1 Jacopo Baldi,1 Megan E Cavet,2 Paolo Govoni,3 Santi Spampinato11Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy; 2Global Pharmaceutical R&D, Bausch & Lomb Inc., Rochester, NY, USA; 3Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, ItalyBackground: Mapracorat, a novel nonsteroidal selective glucocorticoid receptor agonist, has been proposed for the topical treatment of inflammatory disorders as it binds with high affinity and selectivity to the human glucocorticoid receptor and displays a potent anti-inflammatory activity, but seems to be less effective in transactivation of a number of genes, resulting in a lower potential for side effects. Contrary to classical glucocorticoids, mapracorat displays a reduced ability to increase intraocular pressure and in inducing myocilin, a protein linked to intraocular pressure elevation. Allergic conjunctivitis is the most common form of ocular allergy and can be divided into an early phase, developing immediately after allergen exposure and driven primarily by mast cell degranulation, and a late phase, developing from 6–10 hours after the antigen challenge, and characterized by conjunctival infiltration of eosinophils and other immune cells as well as by the production of cytokines and chemokines.Methods: In this study, mapracorat was administered into the conjunctival sac of ovalbumin (OVA-sensitized guinea pigs 2 hours after the induction of allergic conjunctivitis, with the aim of investigating its activity in reducing clinical signs of the late-phase ocular reaction and to determine its mechanism of anti-allergic effects with respect to apoptosis of conjunctival eosinophils and expression of the chemokines C-C motif ligand 5 (CCL5, C-C motif ligand 11 (CCL11, and interleukin-8 (IL-8 and the proinflammatory cytokines interleukin-1β (IL-1β and tumor necrosis factor-α (TNF

Chronic eosinophilic pneumonia: a case report

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Heo, Tae Haeng; Park, Jeong Hee; Lim, Jong Nam; Shin, Hyun Jun; Jeon, Hae Jeong [College of Medicine, Kon-Kuk University, Seoul (Korea, Republic of)

1995-05-15

Chronic eosinophilic pneumonia is a rare disease characterized by chronic infiltration of the lung with eosinophils, usually associated with peripheral eosinophilia. In 65% of cases, the chest radiograph shows typical nonsegmental air-space consolidation confined to the outer third of the lung, and in 25% of cases, the 'photographic negative of pulmonary edema' Typical lung manifestations with peripheral eosinophilia are characteristic of chronic eosinophilic pneumonia. In the remaining cases, radiographic findings are nonspecific and require lung biopsy for confirmation. We report a case of chronic eosinophilic pneumonia in which chest radiograph and CT scans revealed bilateral patchy or diffuse opacity with nodules scattered throughout the lungs.

Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

International Nuclear Information System (INIS)

Ribeiro-Filho, Jaime; Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana; Moraes de Carvalho, Katharinne Ingrid; Silva Mendes, Diego da; Melo, Christianne Bandeira; Martins, Marco Aurélio; Silva Dias, Celidarque da; Piuvezam, Márcia Regina

2013-01-01

Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca ++ influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

Energy Technology Data Exchange (ETDEWEB)

Ribeiro-Filho, Jaime [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Moraes de Carvalho, Katharinne Ingrid [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Mendes, Diego da [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Melo, Christianne Bandeira [Laboratório de Inflamação, Instituto Biofisica Carlos Chagas Filho, UFRJ, Rio de Janeiro (Brazil); Martins, Marco Aurélio [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Dias, Celidarque da [Laboratório de Fitoquímica, Departamento de Ciências Farmacêuticas, UFPB, João Pessoa, Paraíba (Brazil); Piuvezam, Márcia Regina, E-mail: mrpiuvezam@ltf.ufpb.br [Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); and others

2013-11-15

Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response.

Science.gov (United States)

Muniz, Valdirene S; Baptista-Dos-Reis, Renata; Benjamim, Claudia F; Mata-Santos, Hilton A; Pyrrho, Alexandre S; Strauch, Marcelo A; Melo, Paulo A; Vicentino, Amanda R R; Silva-Paiva, Juliana; Bandeira-Melo, Christianne; Weller, Peter F; Figueiredo, Rodrigo T; Neves, Josiane S

2015-01-01

Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S. mansoni) infection. We found that adenosine 5'-diphosphate (ADP) induced human eosinophils to secrete eosinophil peroxidase (EPO) in a P2Y12R dependent manner. However, ADP did not interfere with human eosinophil apoptosis or chemotaxis in vitro. In vivo, C57Bl/6 mice were infected with cercariae of the Belo Horizonte strain of S. mansoni. Analyses performed 55 days post infection revealed that P2Y12R blockade reduced the granulomatous hepatic area and the eosinophilic infiltrate, collagen deposition and IL-13/IL-4 production in the liver without affecting the parasite oviposition. As found for humans, murine eosinophils also express the P2Y12R. P2Y12R inhibition increased blood eosinophilia, whereas it decreased the bone marrow eosinophil count. Our results suggest that P2Y12R has an important role in eosinophil EPO secretion and in establishing the inflammatory response in the course of a S. mansoni infection.

Enterobiliary Fistula as a Complication of Eosinophilic Gastroenteritis: a Case Report

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Kim, Han Myun; Woo, Ji Young [Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

2008-06-15

Eosinophilic gastroenteritis is an uncommon disease with variable clinical features characterized by eosinophilic infiltration. Clinical manifestations range from non-specific gastrointestinal complaints such as nausea, vomiting, crampy abdominal pain, and diarrhea to specific findings such as malabsorption, protein loosing enteropathy, luminal obstruction, eosinophilic ascites and effusion. We report here on a case of eosinophilic gastroenteritis causing enterobiliary fistula which is an extremely unusual complication

Enterobiliary Fistula as a Complication of Eosinophilic Gastroenteritis: a Case Report

International Nuclear Information System (INIS)

Kim, Han Myun; Woo, Ji Young

2008-01-01

Eosinophilic gastroenteritis is an uncommon disease with variable clinical features characterized by eosinophilic infiltration. Clinical manifestations range from non-specific gastrointestinal complaints such as nausea, vomiting, crampy abdominal pain, and diarrhea to specific findings such as malabsorption, protein loosing enteropathy, luminal obstruction, eosinophilic ascites and effusion. We report here on a case of eosinophilic gastroenteritis causing enterobiliary fistula which is an extremely unusual complication

Esophageal trachealization: A feature of eosinophilic esophagitis

International Nuclear Information System (INIS)

AlHussaini, Abdulrahman A; Semaan, Toufic; ElHag, Imad A

2009-01-01

Eosinophilic esophagitis (EE) is an inflammatory condition characterized by intense eosinophilic infiltration of the esophagus. EE is frequently misdiagnosed as gastroesophageal reflux disease. Here, we present a child with EE and a characteristic endoscopic finding, r inged esophagus . An 11-year-old Saudi boy presented with dysphagia for 1 year. He had experienced an intermittent sensation of solid food sticking in his chest, which was relieved by drinking liquids. A barium swallow excluded anatomical causes of dysphagia, but revealed multiple-ringed esophagus. Endoscopy showed a furrowing and trachealizing appearance of the entire esophagus. Hisologically, extensive eosinophilic infiltration was a feature in biopsies obtained from the esophagus. The child responded well to a 2-month course of inhaled fluticasone. Symptoms recurred 3 months after discontinuation of therapy, which necessitated resumption of inhaled fluticasone. The endoscopic appearance of multiple esophageal rings should raise suspicion of EE and be confirmed by esophageal biopsies. (author)

Eosinophilic myocarditis due to Churg-Strauss syndrome with markedly elevated eosinophil cationic protein.

Science.gov (United States)

Hara, Tomoya; Yamaguchi, Koji; Iwase, Takashi; Kadota, Muneyuki; Bando, Mika; Ogasawara, Kozue; Bando, Sachiko; Ise, Takayuki; Niki, Toshiyuki; Ueda, Yuka; Tomita, Noriko; Taketani, Yoshio; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Sata, Masataka

2013-01-01

A 67-year-old woman with asthma visited our hospital with increasing dyspnea and new-onset paresthesia and purpura in her legs. Physical examination showed a wheeze, pretibial edema, and surrounding purpura. Chest X-rays showed cardiac decompensation and an electrocardiogram revealed a new ST-T change. Laboratory data showed leukocytosis, hypereosinophilia (10,450/μL), troponin T(+), elevated BNP, and markedly elevated eosinophil cationic protein (ECP) (> 150 ng/mL). Echocardiography revealed diffuse left ventricular hypokinesis (ejection fraction 30%) with increased wall thickness. Coronary angiography was normal. Cardiac magnetic resonance imaging implied diffuse myocardial edema and subendocardial late gadolinium enhancement. Skin biopsy of purpura showed superfi cial perivascular dermatitis with remarkable eosinophilic infiltrations. No evidence of drug allergies, parasitic infection, or myeloproliferative disorder was detected. Based on these findings, a diagnosis of eosinophilic myocarditis due to Churg-Strauss syndrome was considered. She was administered prednisolone at a dose of 1 mg/kg, cyclophosphamide, and diuretics. Several markers of eosinophilic myocarditis and heart failure gradually improved, including ECP. She was discharged 30 days later with no cardiac event. Eosinophilic myocarditis is characterized by predominantly eosinophilic infi ltration. Eosinophilic granule proteins, such as ECP and major basic protein, play important roles in the pathogenesis of eosinophilic myocarditis. We experienced a rare case of eosinophilic myocarditis due to Churg-Strauss syndrome. Markedly elevated ECP played an important role in the early diagnosis and subsequent reduction in ECP served as a marker of monitoring. In an asthmatic patient with dyspnea, hypereosinophilia, and vasculitis, Churg-Strauss syndrome with eosinophilic myocarditis should be considered.

Eosinophils, probiotics, and the microbiome.

Science.gov (United States)

Rosenberg, Helene F; Masterson, Joanne C; Furuta, Glenn T

2016-11-01

There is currently substantial interest in the therapeutic properties of probiotic microorganisms as recent research suggests that oral administration of specific bacterial strains may reduce inflammation and alter the nature of endogenous microflora in the gastrointestinal tract. Eosinophils are multifunctional tissue leukocytes, prominent among the resident cells of the gastrointestinal mucosa that promote local immunity. Recent studies with genetically altered mice indicate that eosinophils not only participate in maintaining gut homeostasis, but that the absence of eosinophils may have significant impact on the nature of the endogenous gut microflora and responses to gut pathogens, notably Clostridium difficile Furthermore, in human subjects, there is an intriguing relationship between eosinophils, allergic inflammation, and the nature of the lung microflora, notably a distinct association between eosinophil infiltration and detection of bacteria of the phylum Actinobacteria. Among topics for future research, it will be important to determine whether homeostatic mechanisms involve direct interactions between eosinophils and bacteria or whether they involve primarily eosinophil-mediated responses to cytokine signaling in the local microenvironment. Likewise, although is it clear that eosinophils can and do interact with bacteria in vivo, their ability to discern between pathogenic and probiotic species in various settings remains to be explored. © Society for Leukocyte Biology.

Clinical features of so-called eosinophilic rhinosinusitis. With a view to screening for eosinophilic rhinosinusitis

International Nuclear Information System (INIS)

Sakuma, Yasunori; Ishitoya, Junichi; Kimura, Machiko; Hirose, Shouji; Takahashi, Masahiro; Tsukuda, Mamoru

2006-01-01

The concept of so-called eosinophilic sinusitis has recently come to be understood, but since the definition and the diagnostic criteria for this intractable form of sinusitis are unclear, we reviewed the clinical features of 104 patients (16 with eosinophilic sinusitis and 88 with non-eosionphilic sinusitis) who underwent endonasal sinus surgery in our department. So-called eosinophilic sinusitis was usually accompanied by severe bronchial asthma, and the characteristic clinical findings of so-called eosinophilic sinusitis were an increase in peripheral blood eosinophil count, a paranasal sinus shadow in computed tomograms (CT score), and a high ethmoid sinus/maxillary sinus score ratio (E/M ratio) in our study. We determined the cutoff value to review sensitivity, specificity and correct diagnosis rate in screening for eosinophilic sinusitis. When we judged using three cutoff values, a peripheral blood eosinophil count≥500/μ1, CT score≥13 and E/M ratio≥1, a sensitivity of 69%, specificity of 97% and correct diagnosis rate of 81%. On the other hand, when we judged using two cutoff value, peripheral blood eosinophil count≥500/μ1 and E/M ratio≥1, sensitivity of 75%, specificity of 94% and correct diagnosis rate of 88%. Because all three studies can be performed in outpatient clinics, we concluded that they are useful as a method of screening for so-called eosinophilic sinusitis without the need for histological examinations for eosinophil infiltration of nasal polyps in biopsy specimens. (author)

A Non-Frequently Considered Diagnosis of Dysphagia; Eosinophilic Esophagitis

OpenAIRE

Mehmet Ağın; Nilgün Uyduran Ünal; Serdar İskit

2015-01-01

Eosinophilic Esophagitis is infiltration of esophagus mucosa by eosinophil leucocyte. It is rarely observed in children and the symptoms are similar to gastroesophageal reflux. This case, which was applied esophagus balloon dilatation in the pediatric surgery due to dysphagia and diagnosed eosinophilic esophagitis, was presented in order to attract attention to the approach to the child with dysphagia. Total IgE=834 IU/mL and specific IgE (-), Fx5 (-) was found negative. In ...

Mechanisms of eosinophil adhesion to endothelial cells under flow conditions

NARCIS (Netherlands)

Ulfman, L.H.

2002-01-01

Eosinophils play an important role in allergic inflammatory diseases such as allergic asthma. Infiltrates of these cells are present in the interstitium and the lumen of the bronchi of asthmatic patients. Eosinophils must pass the endothelium to enter this site of inflammation. A widely accepted

Immunophenotyping of eosinophils recovered from blood and BAL of allergic asthmatics

NARCIS (Netherlands)

Mengelers, H. J.; Maikoe, T.; Brinkman, L.; Hooibrink, B.; Lammers, J. W.; Koenderman, L.

1994-01-01

Studies of bronchoalveolar lavage (BAL) fluid from patients with allergic asthma have demonstrated active migration of eosinophils into the bronchial lumen after allergen challenge. The mechanisms mediating this eosinophil infiltration and cell activation are largely unexplained. The expression of

Inhibition of NF-κB by a cell permeable form of IκBα induces apoptosis in eosinophils

International Nuclear Information System (INIS)

Fujihara, Satoko; Jaffray, Ellis; Farrow, Stuart N.; Rossi, Adriano G.; Haslett, Christopher; Hay, Ronald T.

2005-01-01

An 11 amino acid HIV-TAT peptide can deliver target proteins into a variety of cells in a receptor-independent manner. To generate a highly specific inhibitor of the transcription factor NF-κB, we have fused the TAT-peptide to a version of IκBα that is resistant to signal-induced degradation. TAT-IκBα(S32A, S36A) inhibited NF-κB-dependent transcription in HeLa and A549 cells by retaining NF-κB p65 in the cytoplasm. Introduction of TAT-IκBα(S32A, S36A) into human eosinophils inhibited the nuclear translocation of NF-κB and induced apoptosis. Thus, continuous NF-κB-dependent transcription is important for eosinophil survival. While eosinophils are normally refractive to standard methods of gene delivery, the ability of TAT fusion proteins to be taken up by these cells should enable a detailed molecular analysis of survival pathways in these cells

Intestinal perforation in a two-year-old child with eosinophilic gastroenteritis

DEFF Research Database (Denmark)

Agertoft, A; Husby, S; Høst, A

1991-01-01

A two-year-old boy underwent a laparatomy for an intestinal perforation due to eosinophilic gastroenteritis. He had marked peripheral blood eosinophilia and a small duodenal biopsy showed heavy eosinophilic infiltration in the mucosa. After 1 1/2 year on a restricted diet, a control duodenal biopsy...... showed only slight eosinophilia. Perforation of the small intestine is a rare but serious complication in eosinophilic gastroenteritis....

Eosinophilic Gastrointestinal Disorder in Coeliac Disease: A Case Report and Review

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Dennis N. F. Lim

2012-01-01

Full Text Available Eosinophilic gastrointestinal disorder is a rare disorder characterised by eosinophilic infiltration of the gastrointestinal tract. There are various gastrointestinal manifestations with eosinophilic ascites being the most unusual and rare presentation. Diagnosis requires high index of suspicion and exclusion of various disorders associated with peripheral eosinophilia. There are no previous case reports to suggest an association between eosinophilic gastrointestinal disorder and coeliac disease in adults. We report a case of eosinophilic ascites and gastroenteritis in a 30-year-old woman with a known history of coeliac disease who responded dramatically to a course of steroids.

Eosinophilic Gastroenteritis Presenting as Intestinal Obstruction - A Case Series

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Amita Krishnappa

2011-07-01

Full Text Available Eosinophilic Gastroenteritis is a rare disease characterized by infiltration of the gastrointestinal tract by an increased number of eosinophils as compared to the normal. The anatomic location and intensity of the infiltrate decides the varied clinical symptomatology with which these patients present. The present report deals with four cases, all presenting with clinical signs of intestinal obstruction A laparotomy performed revealed a stricture in the first case, superficial ulcers and adhesions in the second case, an ileocaecal mass in the third case and volvulus formation in the fourth case. Eosinophilic gastroenteritis was confirmed on histopathology in all the four cases. All the four patients experienced relief of symptoms after resection. It is essential to diagnose the disease to differentiate it from other conditions presenting as intestinal obstruction. The cases are presented because of the rarity of occurrence and presentation. Relevant literature has been reviewed.

Severe Rhabdomyolysis without Systemic Involvement: A Rare Case of Idiopathic Eosinophilic Polymyositis

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Ayesha Farooq

2015-01-01

Full Text Available Introduction. Eosinophilic polymyositis (EPM is a rare cause of rhabdomyolysis characterized by eosinophilic infiltrates in the muscle. We describe the case of a young patient with eosinophilic polymyositis causing isolated severe rhabdomyolysis without systemic involvement. Case Presentation. A 22-year-old Haitian female with no past medical history presented with progressive generalized muscle aches without precipitating factors. Examination of the extremities revealed diffuse muscle tenderness. Laboratory findings demonstrated peripheral eosinophilia and high creatinine phosphokinase (CPK and transaminase levels. Workup for the common causes of rhabdomyolysis were negative. Her CPK continued to rise to greater than 100,000 units/L so a muscle biopsy was performed which showed widespread eosinophilic infiltrate consistent with eosinophilic polymyositis. She was started on high dose systemic corticosteroids with improvement of her symptoms, eosinophilia, and CPK level. Discussion. This case illustrates a systematic workup of rhabdomyolysis in the presence of peripheral eosinophilia. Many differential diagnoses must be considered before establishing a diagnosis of idiopathic eosinophilic polymyositis. To our knowledge, our case of eosinophilic polymyositis is unique as it presented with severe rhabdomyolysis without another organ involvement. Clinicians should maintain a high index of suspicion for this physically debilitating disease to aid in prompt diagnosis.

Inhibition of allergic dermal inflammation by the novel imidazopyridazine derivative TAK-427 in a guinea pig experimental model of eczema.

Science.gov (United States)

Fukuda, Shigeru; Midoro, Katsuo; Kamei, Takayuki; Gyoten, Michiyo; Kawano, Yasuhiko; Ashida, Yasuko; Nagaya, Hideaki

2002-12-01

Antigen challenge by patch ovalbumin emulsion induced an eczema-like skin lesion in epicutaneously sensitized guinea pigs. Diseased skin sites were macroscopically characterized by manifestations of dermatitis, such as erythema, edema, and papules, and microscopically characterized by acanthosis, spongiosis, and dermal infiltration by eosinophils. Using such lesions as a model of eczema, we evaluated the potential value of TAK-427 [2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino] imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate] as a therapeutic agent for atopic dermatitis by comparing it with dexamethasone and antihistamines. TAK-427 (0.3-30 mg/kg, p.o.) and dexamethasone (3 and 10 mg/kg, p.o.) inhibited eosinophil infiltration into the skin and ameliorated the dermatitis manifestations and epidermal damage. By contrast, none of the antihistamines tested (azelastine, ketotifen, terfenadine, and cetirizine) suppressed the eosinophil infiltration or dermatitis manifestations. To elucidate the mechanism by which TAK-427 inhibited the development of eczema, we investigated cytokine expression in the affected skin. Both TAK-427 and dexamethasone suppressed the increased mRNA expression of interleukin (IL)-13, granulocyte-macrophage colony-stimulating factor, IL-1alpha, tumor necrosis factor-alpha, interferon-gamma, and IL-8, but not IL-10, suggesting that TAK-427 inhibits allergic inflammation of the skin leading to the development of eczema by inhibiting the expression of proinflammatory cytokines after antigen challenge.

Clinical and histopathological differential diagnosis of eosinophilic pustular folliculitis.

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Fujiyama, Toshiharu; Tokura, Yoshiki

2013-06-01

Eosinophilic pustular folliculitis (EPF) is an inflammatory disease characterized by repeated pruritic follicular papules and pustules arranged in arcuate plaques, and folliculotropic infiltration of eosinophils. The diagnosis of EPF is occasionally difficult and problematic because EPF may share the clinical appearance and histological findings with other diseases. Moreover, EPF has several clinical subtypes, including the classical type, infantile type and immunosuppression-associated type. Because the therapies of EPF are relatively specific as compared to eczematous disorders, accurate diagnosis is essential for the management of EPF. Clinical differential diagnoses include tinea, acne, rosacea, eczematous dermatitis, granuloma faciale, autoimmune annular erythema, infestations and pustular dermatosis. Histologically, cutaneous diseases with eosinophilic infiltrates can be differentially diagnosed. Follicular mucinosis, mycosis fungoides and other cutaneous T-cell lymphomas are the most important differential diagnoses both clinically and histopathologically. It should be kept in mind particularly that the initial lesions of cutaneous T-cell lymphoma resemble EPF. © 2013 Japanese Dermatological Association.

PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells.

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Jinseon Jeong

Full Text Available Increased number of eosinophils in the circulation and sputum is associated with the severity of asthma. The respiratory epithelium produces chemokine (C-C motif ligands (CCL which recruits and activates eosinophils. A chemically synthesized monoacetyl-diglyceride, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol is a major constituent in the antlers of Sika deer (Cervus nippon Temminck which has been used in oriental medicine. This study was aimed to investigate the molecular mechanism of PLAG effect on the alleviation of asthma phenotypes. A549, a human alveolar basal epithelial cell, and HaCaT, a human keratinocyte, were activated by the treatment of interleukin-4 (IL-4, and the expression of chemokines, known to be effective on the induction of eosinophil migration was analyzed by RT-PCR. The expression of IL-4 induced genes was modulated by the co-treatment of PLAG. Especially, CCL26 expression from the stimulated epithelial cells was significantly blocked by PLAG, which was confirmed by ELISA. The transcriptional activity of signal transducer and activator of transcription 6 (STAT6, activated by IL-4 mediated phosphorylation and nuclear translocation, was down-regulated by PLAG in a concentration-dependent manner. In ovalbumin-induced mouse model, the infiltration of immune cells into the respiratory tract was decreased by PLAG administration. Cytological analysis of the isolated bronchoalveolar lavage fluid (BALF cells proved the infiltration of eosinophils was significantly reduced by PLAG. In addition, PLAG inhibited the migration of murine bone marrow-derived eosinophils, and human eosinophil cell line, EoL-1, which was induced by the addition of A549 culture medium.

Eosinophilic cholecystitis: an infrequent cause of acute cholecystitis

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María del Moral-Martínez

2015-01-01

Full Text Available Eosinophilic cholecystitis (EC is a rare disease that is characterised by eosinophilic infiltration of the gallbladder. Its pathogenesis is unknown, although many hypotheses have been made. Clinical and laboratory manifestations do not differ from those of other causes of cholecystitis. Diagnosis is histological and usually performed after analysis of the surgical specimen. We report the case of a woman aged 24 years, with symptoms of fever, vomiting and pain in the right upper quadrant. When imaging tests revealed acalculous cholecystitis, an urgent cholecystectomy was performed. Histological examination of the surgical specimen revealed eosinophilic cholecystitis. No cause of the symptoms was found.

Total artificial heart implantation for biventricular failure due to eosinophilic myocarditis.

Science.gov (United States)

Kawabori, Masashi; Kurihara, Chitaru; Miller, Yair; Heck, Kent A; Bogaev, Roberta C; Civitello, Andrew B; Cohn, William E; Frazier, O H; Morgan, Jeffrey A

2017-09-01

Idiopathic hypereosinophilic syndrome is a condition of unknown etiology characterized by proliferation of eosinophils and their infiltration into tissues. Although cardiac involvement is rare, eosinophilic myocarditis can lead to life-threating fulminant congestive heart failure. Treatment of patients with eosinophilic myocarditis is challenging as heart failure can be caused by biventricular dysfunction. To our knowledge, this is the first case reported in the literature describing a patient with acute severe biventricular heart failure caused by eosinophilic myocarditis with mural left ventricular apical thrombus who was successfully treated with implantation of a total artificial heart as a bridge to heart transplant.

Airway eosinophils accumulate in the mediastinal lymph nodes but lack antigen-presenting potential for naive T cells

NARCIS (Netherlands)

van Rijt, Leonie S.; Vos, Nanda; Hijdra, Daniëlle; de Vries, Victor C.; Hoogsteden, Henk C.; Lambrecht, Bart N.

2003-01-01

Asthma is characterized by infiltration of the airway wall with eosinophils. Although eosinophils are considered to be effector cells, recent studies have reported their ability to activate primed Th2 cells. In this study, we investigated whether eosinophils are capable of presenting Ag to unprimed

Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle

1999-01-01

-assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used...... age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies...... should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth....

Histopathologic diagnosis of eosinophilic conditions in the gastrointestinal tract.

Science.gov (United States)

Hurrell, Jennifer M; Genta, Robert M; Melton, Shelby D

2011-09-01

Eosinophils, a constitutive component of the columnar-lined gastrointestinal tract, play an essential role in allergic responses and parasitic infections. The tissue density of these cells also increases in a variety of conditions of uncertain etiology. With the exception of the esophageal squamous epithelium, in which no eosinophils are normally present, the population of normal eosinophils in the remainder of the luminal gut is poorly defined. Therefore, histopathologists must rely on their subjective judgment to determine when a diagnosis of eosinophilic gastritis, enteritis, or colitis should be rendered. Eosinophilic esophagitis is currently the best defined and most studied eosinophilic condition of the digestive tract; therefore, the confidence in accurate diagnosis is increasing. In contrast, the characteristic clinicopathologic features of eosinophilic conditions affecting other parts of the digestive tract remain somewhat elusive. This review was designed to present pathologists with simple and practical information for the biopsy-based histopathologic diagnosis of eosinophilic esophagitis, gastritis, enteritis, and colitis. It was prepared by critically reviewing more than 200 articles on the topic, along with incorporating evidence accumulated through our own collective experience. We anticipate that by increasing pathologists' confidence in reporting these abnormal but often nameless eosinophilic infiltrates, we can help better define and characterize their significance.

Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs.

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Julie G Ledford

Full Text Available Surfactant protein-A (SP-A has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. In the current study, we used an in vivo model with wild type (WT and SP-A(-/- allergic mice challenged with the model antigen ovalbumin (Ova that were concurrently infected with Mp (Ova+Mp to test the hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products. SP-A deficient mice exhibit significant increases in inflammatory cells, mucus production and lung damage during concurrent allergic airway disease and infection (Ova+Mp as compared to the WT mice of the same treatment group. In contrast, SP-A deficient mice have significantly decreased Mp burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase (EPO, which has been implicated in pathogen killing and also in epithelial dysfunction due to oxidative damage of resident lung proteins, is enhanced in samples from allergic/infected SP-A(-/- mice as compared to WT mice. In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity. These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation

Peritumoral eosinophils predict recurrence in colorectal cancer.

Science.gov (United States)

Harbaum, Lars; Pollheimer, Marion J; Kornprat, Peter; Lindtner, Richard A; Bokemeyer, Carsten; Langner, Cord

2015-03-01

In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; Peosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58-0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52-0.93; P=0.01)-independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients independent of the overall tumor-associated inflammatory response. Evaluation of peritumoral eosinophils represents a promising

Eosinophilic colitis in infants.

Science.gov (United States)

Lozinsky, Adriana Chebar; Morais, Mauro Batista de

2014-01-01

To review the literature for clinical data on infants with allergic or eosinophilic colitis. MEDLINE search of all indexes was performed using the words "colitis or proctocolitis and eosinophilic" or "colitis or proctocolitis and allergic" between 1966 and February of 2013. All articles that described patients' characteristics were selected. A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263) of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 per high-power field) in 89.3% (236/264) of patients. Most patients showed improvement with the removal of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients). Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow's milk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Eosinophilic colitis in infants

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Adriana Chebar Lozinsky

2014-01-01

Full Text Available OBJECTIVE: To review the literature for clinical data on infants with allergic or eosinophilic colitis. DATA SOURCE: MEDLINE search of all indexes was performed using the words ''colitis or procto-colitis and eosinophilic'' or ''colitis or proctocolitis and allergic'' between 1966 and February of 2013. All articles that described patients' characteristics were selected. DATA SYNTHESIS: A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263 of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 perhigh-power field in 89.3% (236/264 of patients. Most patients showed improvement with theremoval of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients. CONCLUSIONS: Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow'smilk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure.

Eosinophilic esophagitis: manometric and pHmetric findings

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Monica Maria Cardoso Monnerat

2012-06-01

Full Text Available CONTEXT: Eosinophilic esophagitis is an entity characterized by an esophageal inflammatory infiltrate of eosinophils, manifested by dysphagia, intermittent food impactions and symptoms similar to gastroesophageal reflux disease (GERD, that predominantly affects young adults. There may be association of eosinophilic esophagitis with GERD, and motor abnormalities have been described. OBJECTIVE: The main objectives of this study are to describe the findings at esophageal manometry and pH monitoring in patients with eosinophilic esophagitis. METHODS: Cross-sectional study of 20 patients with a diagnosis of eosinophilic esophagitis, submitted to esophageal manometry and 24h pH monitoring. Were analysed the manometric changes and the presence of abnormal reflux on pH monitoring. RESULTS: Twenty patients (15 men, 5 women had a mean age of 29 years. Motility disorders were found in 25% (5/20 patients with ineffective esophageal motility being the most common finding. pH monitoring revealed abnormal reflux on 25%, without any relationship with manometric findings. CONCLUSIONS: Manometric abnormalities were observed in 25% of patients and abnormal reflux on pH monitoring also in 25%. This study showed no relationship between abnormal reflux and the presence of manometric changes.

Changes in CD11b and L-selectin expression on eosinophils are mediated by human lung fibroblasts in vitro

NARCIS (Netherlands)

Spoelstra, FM; Hovenga, H; Noordhoek, JA; Postma, DS; Kauffman, HF

Eosinophilic airway infiltration is a central feature in asthma. Eosinophils recovered from bronchoalveolar fluid show an activated phenotype, e.g., increased CD11b and decreased L-selectin expression. We investigated whether lung fibroblasts are able to activate eosinophils in vitro, and if so,

Feline familial pedal eosinophilic dermatosis in two littermates

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Charline Pressanti

2015-04-01

Full Text Available In cats, the most common eosinophilic dermatoses are feline miliary dermatitis and eosinophilic granuloma complex. The most commonly identified underlying cause is a hypersensitivity reaction. Few cases of familial forms of eosinophilic dermatoses are reported in the literature. Two young adult cats from the same litter presented 2 years apart with a severe and chronic fluid or tissue infiltration of the distal part of several limbs. Lesions started on the forelegs and developed on the other limbs. Cytological and histopathological examinations showed lesions consistent with an atypical form of feline eosinophilic dermatosis associated with secondary bacterial infection. In both cats, antibiotics combined with immunosuppressive treatment partially improved the lesions, which continued to progress on a waxing and waning course, even in the absence of treatment. Allergy work-up did not permit the identification of an underlying allergic triggering factor. The severity of the lesions, the unusual presentation and the unsatisfactory response to immunosuppressive therapy in two feline littermates suggested a genetic form of eosinophilic dermatosis.

PGD2 induces eotaxin-3 via PPARγ from sebocytes: a possible pathogenesis of eosinophilic pustular folliculitis.

Science.gov (United States)

Nakahigashi, Kyoko; Doi, Hiromi; Otsuka, Atsushi; Hirabayashi, Tetsuya; Murakami, Makoto; Urade, Yoshihiro; Zouboulis, Christos C; Tanizaki, Hideaki; Egawa, Gyohei; Miyachi, Yoshiki; Kabashima, Kenji

2012-02-01

Eosinophilic pustular folliculitis (EPF) is a chronic intractable pruritic dermatosis characterized by massive eosinophil infiltrates involving the pilosebaceous units. Recently, EPF has been regarded as an important clinical marker of HIV infection, and its prevalence is increasing in number. The precise mechanism by which eosinophils infiltrate into the pilosebaceous units remains largely unknown. Given that indomethacin, a COX inhibitor, can be successfully used to treat patients with EPF, we can assume that COX metabolites such as prostaglandins (PGs) are involved in the etiology of EPF. To determine the involvement of PGs in the pathogenesis of EPF. We performed immunostaining for PG synthases in EPF skin lesions. We examined the effect of PGD(2) on induction of eotaxin, a chemoattractant for eosinophils, in human keratinocytes, fibroblasts, and sebocytes and sought to identify its responsible receptor. Hematopoietic PGD synthase was detected mainly in infiltrating inflammatory cells in EPF lesions, implying that PGD(2) was produced in the lesions. In addition, PGD(2) and its immediate metabolite 15-deoxy-Δ 12,14-PGJ(2) (15d-PGJ(2)) induced sebocytes to produce eotaxin-3 via peroxisome proliferator-activated receptor gamma. Consistent with the above findings, eotaxin-3 expression was immunohistochemically intensified in sebaceous glands of the EPF lesions. The PGD(2)/PGJ(2)-peroxisome proliferator-activated receptor gamma pathway induces eotaxin production from sebocytes, which may explain the massive eosinophil infiltrates observed around pilosebaceous units in EPF. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Topical corticosteroids do not revert the activated phenotype of eosinophils in eosinophilic esophagitis but decrease surface levels of CD18 resulting in diminished adherence to ICAM-1, ICAM-2, and endothelial cells.

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Lingblom, Christine; Bergquist, Henrik; Johnsson, Marianne; Sundström, Patrik; Quiding-Järbrink, Marianne; Bove, Mogens; Wennerås, Christine

2014-12-01

Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

Eosinophilic Gastroenteritis as a Rare Cause of Recurrent Epigastric Pain

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Mohammad Taghi Safari

2016-04-01

Full Text Available Eosinophilic gastroenteritis (EGE is a rare inflammatory disorder of gastrointestinal tract characterized by eosinophilic infiltration of the bowel wall. It can mimic many gastrointestinal disorders due to its wide spectrum of presentations. Diagnose is mostly based on excluding other disorders and a high suspicion. Here we report a case of 26 year old man with a history of sever epigastric pain followed by nausea, vomiting since a few days before admission with final diagnosis of EGE.

Activated Eosinophils are Present in Esophageal Muscle in Patients with Achalasia of the Esophagus

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Jin, Hong; Wang, Bin; Zhang, Li-li

2018-01-01

Background The aim of this study was to undertake a histological evaluation of the presence of eosinophils in esophageal muscle in patients with achalasia before treatment with peroral endoscopic myotomy (POEM), with clinical follow-up at one year. Material/Methods Before treatment, esophageal biopsies including mucosa and esophageal muscle were obtained from 28 patients with achalasia. Nine patients who had undergone esophagectomy for esophageal carcinoma were included in the control group. The Eckardt Score was used to evaluate the clinical symptoms of achalasia. Histology of routinely processed tissue sections was used to perform eosinophil cell counts (0 to +++), and immunohistochemistry was used to detect expression of eosinophil major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and S100 protein in cases of achalasia (n=28) and controls (n=9). The findings in patients with achalasia were compared before and one year following POEM. Results Esophageal tissue from patients with achalasia showed eosinophils infiltrating into the muscularis externa in 85.7% (24/28), into the muscularis propria in 28.6% (8/28), and in 89% (25/28) there were few remaining myenteric ganglion cells, before POEM. The extent of inflammation was similar in all regions of the esophagus and between subtypes of achalasia. At one year following POEM, the Eckardt Scores between the former eosinophil (0) group and the eosinophil (+++) group were significantly different (Z=3.50, P=0.030). Conclusions Achalasia of the esophagus was associated with infiltration of the esophageal muscle by activated eosinophils and a decrease in the density of ganglion cells in the myenteric esophageal plexus. PMID:29672471

High-resolution CT in eosinophilic granuloma (histiocytosis X) of the lung

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Godwin, J.D.; Buschman, D.L.; Moore, A.D.A.; Muller, N.L.; Naidich, D.P.; Carvalho, C.R.R.; Takasugi, J.E.; Schmidt, R.A.

1988-01-01

Eosinophilic granuloma of the lung is fascinating but poorly understood. Computed tomographic (CT) scans in 18 cases (11 high resolution) showed a variety of striking patterns: cysts up to 4 cm with thin or indiscernible walls, ranging from a few lesions to confluent honeycombing; retriculonodular infiltrate; and nodules 2 mm-2cm, sometimes cavitated. CT showed that the ill-defined lucencies barely visible on radiographs are indeed cysts, rather than preserved normal lung surrounded by infiltrate. High-resolution CT showed that some of the early, small nodules were concentrated along terminal bronchioles within the secondary lobules. The differential diagnosis includes sarcoidosis and idiopathic fibrosis, but the prominent cystic abnormality and the lack of peripheral concentration help to distinguish eosinophilic granuloma

Canine eosinophilic folliculitis and furunculosis in three cases.

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Curtis, C F; Bond, R; Blunden, A S; Thomson, D G; McNeil, P E; Whitbread, T W

1995-03-01

The historical, clinical and histopathological features of three dogs with eosinophilic folliculitis and furunculosis are described. The disease was characterised by the rapid development of pruritic, papular, pustular and ulcerative lesions on the dorsum of the muzzle. Skin lesions were confined to the face in two cases. The third dog had more generalised pustular lesions. Skin biopsy specimens showed marked eosinophil infiltration particularly centred on pilosebaceous units. Dermal collagen necrosis was evident in two cases. Similar facial lesions have previously been described as 'nasal pyoderma'. The three dogs failed to respond to initial antibacterial therapy but showed a rapid clinical response when prednisolone was given orally at doses ranging from 1 to 2.2 mg/kg, in addition to the antibacterial therapy, suggesting that glucocorticoids are indicated for the treatment of eosinophilic folliculitis and furunculosis. The aetiology of the disease was not determined.

[Non allergic simple eosinophilic pneumonia--Löffler syndrome--a case report study].

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Meta-Jevtović, Ivana; Tomović, Miroslav S; Mojsilović, Slavica; Petrović, Marina

2008-01-01

Löffler syndrome is an acute, pneumonia of unknown ethiology. This disease is not often associated with bronchial asthma. In its asymptomatic form, this disease is reversible, transient, self-limited with no requests for specific therapy regimen. In the symptomatic form, as well as during its progression, treatment with steroids is very effective. Furthermore, in both acute eosinophilic and idiopathic chronic eosinophilic form, this kind of therapy ensures survival. The case of a 53-year-old Caucasian woman was presented with 2-month history of low grade fever, shortness of breath, cough and reduced exercise tolerance. Although she had an allergic accident on insects in history, non allergy reactions as well as an obstructive disease with that kind of origin were not detected on admission. The diagnosis of simple eosinophilic pneumonia (SEP) (Löffler's syndrome) was confirmed by transbronchial biopsy and by sternal testing. The peripheral blood eosinophilia with pulmonary eosinophilic infiltrates on X ray chest radiography were observed during clinical examination. Biopsy specimen of the lung parenchym showed changes associated with Löffler's syndrome. The diagnosis was, also, confirmed according to the radiographic findings of unilateral migratory infiltrates consistent pneumonia. Churg Strauss syndrome (CSS) has to be considered in this differential diagnosis. Frequently, this disease has extrinsic bronchial asthma with eosinophilic pneumonia in history: asthma is often associated with allergic bronchopulmonary aspergillosis. In the reported case, treatment with steroids resulted in a marked clinical improvement compared to nonsteroid therapy.

Down modulation of L-Selectin expression on eosinophils recovered from bronchoalveolar lavage fluid after allergen provocation

NARCIS (Netherlands)

Mengelers, H. J.; Maikoe, T.; Hooibrink, B.; Kuypers, T. W.; Kreukniet, J.; Lammers, J. W.; Koenderman, L.

1993-01-01

In allergic asthma eosinophils infiltrate into the lung after allergen challenge. The mechanism of this cellular infiltration is not fully understood. L-Selectin is involved in leucocyte-endothelial cell recognition and participates in homing of leucocytes into sites of inflammation. To find

Eosinophilic ascites due to severe eosinophilic ileitis.

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Setia, Namrata; Ghobrial, Peter; Liron, Pantanowitz

2010-09-17

There is a broad etiology for effusion eosinophilia that includes allergic, reactive, infectious, immune, neoplastic, and idiopathic causes. We report and describe the cytomorphologic findings of a rare case of eosinophilic ascites due to severe eosinophilic ileitis. A 17-year-old male manifested acutely with eosinophilic ascites due to severe biopsy-proven subserosal eosinophilic ileitis. Isolated peritoneal fluid submitted for cytologic evaluation revealed that 65% eosinophils were present in a bloody background. The patient responded to corticosteroids, with complete resolution of his ascites. Eosinophilic gastroenteritis with subserosal involvement should be added to the list of causes for eosinophils in peritoneal fluid. The finding of eosinophilic ascites, with appropriate clinical and laboratory findings, may warrant the need to perform laparoscopic intestinal biopsies to confirm the diagnosis.

Eosinophilic Oesophagitis in Infants and Children in the Region of Southern Denmark: A Prospective Study of Prevalence and Clinical Presentation

DEFF Research Database (Denmark)

Dalby, Kasper; Nielsen, Rasmus G; Kruse-Andersen, Soren

2010-01-01

OBJECTIVE:: Eosinophilic oesophagitis (EE) is a clinical entity characterised by a set of symptoms and eosinophilic infiltration of the oesophageal epithelium. Recent reports indicate that EE is increasingly diagnosed in paediatric patients. We aimed to evaluate the epidemiology of paediatric EE...

Eosinophilic ascites due to severe eosinophilic ileitis

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Setia Namrata

2010-01-01

Full Text Available Background: There is a broad etiology for effusion eosinophilia that includes allergic, reactive, infectious, immune, neoplastic, and idiopathic causes. We report and describe the cytomorphologic findings of a rare case of eosinophilic ascites due to severe eosinophilic ileitis. Case Presentation: A 17-year-old male manifested acutely with eosinophilic ascites due to severe biopsy-proven subserosal eosinophilic ileitis. Isolated peritoneal fluid submitted for cytologic evaluation revealed that 65% eosinophils were present in a bloody background. The patient responded to corticosteroids, with complete resolution of his ascites. Conclusion: Eosinophilic gastroenteritis with subserosal involvement should be added to the list of causes for eosinophils in peritoneal fluid. The finding of eosinophilic ascites, with appropriate clinical and laboratory findings, may warrant the need to perform laparoscopic intestinal biopsies to confirm the diagnosis.

EOSINOPHILIC INFLAMMATORY DISEASES OF THE GASTROINTESTINAL TRACT AND FOOD ALLERGY AMONG CHILDREN

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P.V. Shumilov

2007-01-01

Full Text Available Within the structure of the inflammatory diseases of the gastrointestinal tract among children, one may single out a specific group of the chronic pathology of the digestive apparatus — eosinophilic diseases of the gastrointestinal tract and gastroenterological manifestations of the food allergy. The food allergy is characterized by the pathologic immune reactivity among commonly genetically predisposed people. Depending on the peculiarities of the immune reactivity of a sick person and the nature of the allergen, the allergic reaction may evolve with primary involvement of the different mechanisms or th2 IgE-mediated, or Th1 non-igecmediated. Clinical picture of the food allergy is the manifestation of the immunoinflammatory process caused by the interaction of the food antigens with the structures of the lymphoid tissues associated with the mucous membranes of this or that target organ. The morphological basis of the clinical picture is mostly immune inflammation with primarily eosinophilic tissue infiltration. The eosinophilic lesions of the gastrointestinal tract include eosinophilic esophagitis, eosinophilic gastroenteritis, eosinophilic enteritis, eosinophilic colitis, eosinophilic proctitis and other states. During the food allergy each of the clinical forms of the gastrointestinal tract lesion has its own peculiarities with regards to the primary development mechanism, age of manifestation, character of the run and behaviour tactics.Key words: eosinophilic inflammation, esophagitis, gastroenteritis, colitis, food allergy.

Racial differences in eosinophilic gastrointestinal disorders among Caucasian and Asian

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Jun Ito

2015-07-01

Conclusions: We found that EoE occurs more frequently in Caucasian EGID patients than Asian EGID patients, while the reverse is true for EGE. Also, racial disparities in symptoms and eosinophil-infiltrated tissues were observed. Our findings suggest further genetic and environmental studies to elucidate the etiology of EGID.

Scleroderma mimicker – Eosinophilic fasciitis

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Debanjali Sinha

2017-01-01

Full Text Available Eosinophilic fasciitis is an uncommon connective tissue disorder characterized by thickening of the deep fascia and overlying skin and subcutaneous tissue. It may mimic scleroderma and other scleroderma-like conditions. It may be a manifestation of paraneoplastic disorders or may be associated with hematological disorders including lymphomas. Definitive diagnosis is made on histological examination of a deep skin biopsy revealing thickened deep fascia and infiltration by lymphocytes and eosinophils. Enhancement of deep fascia on Gadolinium contrast-enhanced magnetic resonance imaging may be used as a substitute for skin biopsy. Ultrasound imaging is an evolving imaging tool for diagnosing it. Glucocorticoids with or without immunosuppressive agents remains the mainstay of therapy with good response, generally. A younger age of onset, morphea like lesions and dermal fibrosclerosis is more likely to be associated with the refractory disease. Early diagnosis and appropriate treatment may result in better outcomes in terms of morbidity and quality of life of the patients.

Eosinophilic esophagitis: an Italian experience Esofagitis eosinofílica: una experiencia italiana

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C. Vindigni

2010-01-01

Full Text Available Background: eosinophilic esophagitis is an esophageal disorder characterized by esophageal and/or upper gastrointestinal tract symptoms, and by dense esophageal eosinophilia associated with a normal gastric and duodenal mucosa. Prevalently reported in children, eosinophilic esophagitis has recently been reported with increased frequency also in adults. Aims: the purpose of this study was to report our experience with eosinophilic esophagitis in Italy, since there are only very few series of such patients in our country. Patients and methods: we retrospectively reviewed the histological data of consecutive patients with a diagnosis of esophagitis or reflux disease in the period September 2004-September 2008. Eosinophils were counted where they appeared most numerous in the biopsy, with a cutoff > 15 eosinophils in more than one high-power field as diagnostic of eosinophilic esophagitis. Patients were excluded if gastric or duodenal biopsies showed a prominent eosinophilic infiltrate. Results: twenty two patients (14 adults, 8 children, age range 2-59 years were identified according to the above criteria. The average eosinophil count was 86/ high-power field (range 31-150, associated with other pathologic features (eosinophilic microabscesses eosinophil degranulation, basal zone hyperplasia, papillary elongation. The main clinical complaints were dysphagia, food impaction, and heartburn, and endoscopic findings consisted of mucosal thickening and inelasticity, longitudinal shearing, rings, and white specks, without difference between adults and children for both clinical and endoscopic variables. Conclusions: eosinophilic esophagitis is not rare in Italy, and displays clinical, endoscopic, and pathologic features similar to those described in other countries.

Eosinophilic Disorders

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... eosinophils per microliter of blood). Low number of eosinophils A low number of eosinophils in the blood ( ... the normal number of eosinophils. High number of eosinophils The most common causes of a high number ...

Eosinophilic granulomatosis with polyangiitis: an overview

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Andrea eGioffredi

2014-11-01

Full Text Available Eosinophilic granulomatosis with polyangiitis (EGPA is a multisystemic disorder, belonging to the small vessel ANCA-associated vasculitis, defined as a eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract, and necrotizing vasculitis predominantly affecting small to medium-sized vessels, associated with asthma and eosinophilia. EGPA pathogenesis is not well known: HLA-DRB1*04 and *07, HLA-DRB4 and IL10.2 haplotype of the IL-10 promoter gene are the most studied genetic determinants. Among the acquired pathogenetic factors, the exposure to different allergens, infections, vaccinations, drugs and silica exposure have been involved.Eosinophils are the most characteristic cells in EGPA and different studies have demonstrated their role as effector and immunoregulatory cells.EGPA is considered a disease with a prevalent activation of the Th2 cellular-mediated inflammatory response but also humoral immunity plays an important role. A link between B and T inflammatory responses may explain different disease features. EGPA typically develops into three sequential phases: the allergic phase, distinguished by the occurrence of asthma, allergic rhinitis and sinusitis, the eosinophilic phase, in which the main pathological finding is the eosinophilic organ infiltrations (e.g. lungs, heart and gastrointestinal system and the vasculitic phase, characterized by purpura, peripheral neuropathy and constitutional symptoms.ANCA (especially pANCA anti-MPO are present in 40-60% of the patients. An elevation of IgG4 is frequently found. Corticosteroids and cyclophosphamide are classically used for remission induction, while azathioprine and methotrexate are the therapeutic options for remission maintenance. B-cell depletion with rituximab has shown promising results for remission induction.

Alveolar occupation infiltrations, eosinophilia in peripheral blood and bronchoalveolar lavage

International Nuclear Information System (INIS)

Hincapie Diaz, Gustavo Adolfo; Yama Mosquera, Erica; Guevara, Jairo

2006-01-01

A case of a patient of 25 years old is shown with the antecedent of no potable water consumption who entered for having pulmonary symptoms, fever, presence of alveolar occupation infiltrations and eosinophilia in peripheral blood treatment with antiparasitary started with a significant improvement of the symptoms, infiltrations and eosinophilia. It is considered eosinophilic pneumonia diagnostic by parasitary infection (Loefffers Syndrome)

Alveolar occupation infiltrations, eosinophilia in peripheral blood and bronchoalveolar lavage

International Nuclear Information System (INIS)

Hincapie Diaz, Gustavo Adolfo; Yama Mosquera, Erica; Guevara, Jairo

2006-01-01

A case of a patient of 25 years old is shown with the antecedent of no potable water consumption who entered for having pulmonary symptoms. Fever, presence of alveolar occupation infiltrations and eosinophilia in peripheral blood a treatment with antiparasitary started with a significant improvement of the symptoms, infiltrations and eosinophilia. it is considered eosinophilic pneumonia diagnostic by parasitary infection (Loeffler's syndrome)

Eosinophilic myositis as first manifestation in a patient with type 2 myotonic dystrophy CCTG expansion mutation and rheumatoid arthritis.

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Meyer, Alain; Lannes, Béatrice; Carapito, Raphaël; Bahram, Seiamak; Echaniz-Laguna, Andoni; Geny, Bernard; Sibilia, Jean; Gottenberg, Jacques Eric

2015-02-01

Eosinophilic myositis is characterized by eosinophilic infiltration of skeletal muscles. In the absence of an identifiable causative factor or source (including parasitic infection, intake of drugs or L-tryptophan, certain systemic disorders as well as malignant diseases), the diagnosis of idiopathic eosinophilic myositis is usually retained. However, some muscular dystrophies have been recently identified in this subset of eosinophilic myositis. Here, we report a patient with an 8 kb CCTG expansion in intron 1 of the CNBP gene, a mutation characteristic of myotonic dystrophy type 2 (DM2), whose first manifestation was "idiopathic" eosinophilic myositis. This report suggests that in "idiopathic" eosinophilic myositis, clinicians should consider muscular dystrophies, including DM2. Copyright © 2014 Elsevier B.V. All rights reserved.

Detection of eosinophilic myocarditis using contrast-enhanced magnetic resonance imaging: case report

International Nuclear Information System (INIS)

Takahashi, N.; Murakami, Y.; Shimada, T.; Kashima, Y.; Nakamura, K.; Inoue, S.-I.; Sugamori, T.; Katoh, H.; Ishibashi, Y.; Maruyama, R.

2001-01-01

Hypereosinophilic syndrome is characterized by idiopathic eosinophilia in the peripheral blood and multiorgan dysfunction secondary to mature eosinophil infiltration. It is essential to diagnose myocardial involvement in the early stage of the disease when active myocarditis due to cardiotoxic substances from eosinophils is still taking place, but clinical tools for the diagnosis of myocardial lesions in patients without overt cardiac dysfunction are not yet available. We present a case of successful detection of myocarditis due to hypereosinophilic syndrome by gadolinium-diethylenetriaminepentaascetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI). (author)

Detection of eosinophilic myocarditis using contrast-enhanced magnetic resonance imaging: case report

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Takahashi, N.; Murakami, Y.; Shimada, T.; Kashima, Y.; Nakamura, K.; Inoue, S.-I.; Sugamori, T.; Katoh, H.; Ishibashi, Y. [Shimane Medical Univ., The Fourth Dept. of Internal Medicine, Izumo City, Shimane (Japan); Maruyama, R. [Shimane Medical Univ., Dept. of Laboratory Medicine, Izumo City, Shimane (Japan)

2001-02-01

Hypereosinophilic syndrome is characterized by idiopathic eosinophilia in the peripheral blood and multiorgan dysfunction secondary to mature eosinophil infiltration. It is essential to diagnose myocardial involvement in the early stage of the disease when active myocarditis due to cardiotoxic substances from eosinophils is still taking place, but clinical tools for the diagnosis of myocardial lesions in patients without overt cardiac dysfunction are not yet available. We present a case of successful detection of myocarditis due to hypereosinophilic syndrome by gadolinium-diethylenetriaminepentaascetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI). (author)

Leukotriene B4 receptors on guinea pig alveolar eosinophils

International Nuclear Information System (INIS)

Maghni, K.; de Brum-Fernandes, A.J.; Foeldes-Filep, E.G.; Gaudry, M.; Borgeat, P.; Sirois, P.

1991-01-01

The existence of receptors for LTB4 on highly purified guinea pig alveolar eosinophils was investigated. Massive infiltration of eosinophils in alveolar spaces was induced in guinea pigs by i.v. injections of Sephadex beads G50 (16 mg/kg). Alveolar eosinophils (50 x 10(6) cells) were purified to approximately 98% by Percoll continuous density gradient centrifugation. The binding studies indicated that alveolar eosinophils bind LTB4 in a saturable, reversible and specific manner. Scatchard analysis indicated the existence of high-affinity binding sites (Kd1 = 1.00 ± 0.22 nM; Bmax1 = 966 ± 266 sites/cell) and low-affinity binding sites (Kd2 = 62.5 ± 8.9 nM; Bmax2 = 5557 ± 757 sites/cell). The metabolism of LTB4 by alveolar eosinophils in binding conditions was assessed by RP-HPLC and no significant degradation of [3H]LTB4 was observed. LTB4 dose-dependently stimulated eosinophil migration in both chemokinesis and chemotaxis assays with an EC50 value of 1.30 ± 0.14 and 18.14 ± 1.57 nM, respectively. LTB4 caused a dose-dependent increase in the production of superoxide anion with an apparent EC50 value of 50 x 10(-9) M in the authors experimental conditions. LTB4 also induced a dose-dependent increase in the generation of TxA2 with an EC50 value of 46.2 x 10(-9) M. Taken together, their results demonstrated that guinea pig alveolar eosinophils express two classes of specific receptors for LTB4. The high-affinity binding sites seem associated to chemokinesis and chemotaxis whereas the low-affinity binding sites seem associated to superoxide anion production and generation of TxA2. The existence of LTB4 receptors in eosinophils could explain the presence of these cells in hypersensitivity reactions

Investigation of CT diagnostic imaging of 'Eosinophilic chronic rhinosinusitis'

International Nuclear Information System (INIS)

Ogino, Nobuhiro; Matsuwaki, Yoshinori; Ojiri, Hiroya; Kanou, Asami; Fukuda, Kunihiko

2011-01-01

'Eosinophilic chronic rhinosinusitis (ECRS)' is a newly developed entity of chronic rhinosinusitis, which shows resistance against conventional treatment and poor prognosis. Pathologically, ECRS is manifested by high-degree of eosinophilic infiltration in the paranasal sinus mucosa. We structure the CT diagnostic criteria of ECRS and assess its availability. This diagnostic criteria consists of disease distribution (bilateral and predominant in the ethmoid sinus), existence of nasal polyp (s) and high attenuation which suggestive of allergic mucine. We retrospectively review CT of clinically diagnosed 14 ECRS cases to see if CT features of each case fit the criteria or not. The current CT diagnostic criteria of ECRS were proven to be useful to evaluate cases with clinical suspicion of ECRS. (author)

Clinical manifestations, treatment, and outcomes of children and adolescents with eosinophilic esophagitis

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Maraci Rodrigues

2013-03-01

Conclusions: The classic form of EoE typically shows different symptoms according age range. A significant number of patients required more than one treatment cycle to show clinical remission. Endoscopic and histologic improvement was observed; however, eosinophilic infiltration persisted in some patients.

Exosomes from eosinophils autoregulate and promote eosinophil functions.

Science.gov (United States)

Cañas, José Antonio; Sastre, Beatriz; Mazzeo, Carla; Fernández-Nieto, Mar; Rodrigo-Muñoz, José Manuel; González-Guerra, Andrés; Izquierdo, Manuel; Barranco, Pilar; Quirce, Santiago; Sastre, Joaquín; Del Pozo, Victoria

2017-05-01

Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma ( n = 58) and healthy volunteers ( n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals. Reactive oxygen species (ROS) were evaluated by flow cytometry with an intracellular fluorescent probe and nitric oxide (NO) and a colorimetric kit. In addition, exosomal proteins were analyzed by mass spectrometry. Eosinophil-derived exosomes induced an increase in NO and ROS production on eosinophils. Moreover, exosomes could act as a chemotactic factor on eosinophils, and they produced an increase in cell adhesion, giving rise to a specific augmentation of adhesion molecules, such as ICAM-1 and integrin α2. Protein content between exosomes from healthy and asthmatic individuals seems to be similar in both groups. In conclusion, we found that exosomes from the eosinophils of patients with asthma could modify several specific eosinophil functions related to asthma pathogenesis and that they could contribute fundamentally to the development and maintenance of asthma. © Society for Leukocyte Biology.

Cutting Edge: Eosinophils Undergo Caspase-1-Mediated Pyroptosis in Response to Necrotic Liver Cells.

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Palacios-Macapagal, Daphne; Connor, Jane; Mustelin, Tomas; Ramalingam, Thirumalai R; Wynn, Thomas A; Davidson, Todd S

2017-08-01

Many chronic liver disorders are characterized by dysregulated immune responses and hepatocyte death. We used an in vivo model to study the immune response to necrotic liver injury and found that necrotic liver cells induced eosinophil recruitment. Necrotic liver induced eosinophil IL-1β and IL-18 secretion, degranulation, and cell death. Caspase-1 inhibitors blocked all of these responses. Caspase-1-mediated cell death with accompanying cytokine release is the hallmark of a novel form of cell death termed pyroptosis. To confirm this response in a disease model, we isolated eosinophils from the livers of Schistosoma mansoni -infected mice. S. mansoni eggs lodge in the hepatic sinusoids of infected mice, resulting in hepatocyte death, inflammation, and progressive liver fibrosis. This response is typified by massive eosinophilia, and we were able to confirm pyroptosis in the infiltrating eosinophils. This demonstrated that pyroptosis is a cellular pathway used by eosinophils in response to large-scale hepatic cell death. Copyright © 2017 by The American Association of Immunologists, Inc.

Eritema anular eosinofílico en un adulto Eosinophilic anular erythema in an adult.

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Lobo, Marta Aguado; Gonzalo, Elena Sierra; Jiménez-Reyes, José

2017-10-15

Eosinophilic annular erythema (EAE) is an uncommon eosinophilic dermatosis. Clinically it is characterized by recurrent episodes of annular or figurative plaques. The histopathological study shows a perivascular inflammatory infiltrate in the superficial and deep dermis, composed of lymphocytes and eosinophils. It was originally described in children. We report an adult woman who presented with recurrent erythematous annular plaques on the trunk and extremities. A biopsy showed a mainly perivascular lymphocytic infiltrate with numerous eosinophils in the dermis. Laboratory examinations revealed subclinical hypothyroidism. The lesions resolved with topical corticosteroid spontaneously after 3 months.El eritema anular eosinofílico (EAE) es una dermatosis eosinofílica poco frecuente. Clínicamente se caracteriza por episodios recurrentes de placas anulares o figuradas.El estudio histopatológico muestra un infiltrado inflamatorio en dermis superficial y profunda, de localización perivascular y compuesto por linfocitos y eosinófilos. Se describió originariamente en niños. Presentamos una mujer adulta con episodios recurrentes de placas anulares o figuradas en el tronco y extremidades. La biopsia mostró un infiltrado linfocítico perivascular con numerosos eosinófilos en la dermis. La analítica reveló la presencia de hipotiroidismo subclínico. Las lesiones se resolvieron después de tres meses de tratamiento con una crema de corticoesteriodes.

BRAF inhibition is associated with increased clonality in tumor-infiltrating lymphocytes

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Cooper, Zachary A; Frederick, Dennie T; Juneja, Vikram R; Sullivan, Ryan J; Lawrence, Donald P; Piris, Adriano; Sharpe, Arlene H; Fisher, David E; Flaherty, Keith T; Wargo, Jennifer A

2013-01-01

There have been significant advances with regard to BRAF-targeted therapies against metastatic melanoma. However, the majority of patients receiving BRAF inhibitors (BRAFi) manifest disease progression within a year. We have recently shown that melanoma patients treated with BRAFi exhibit an increase in melanoma-associated antigens and in CD8+ tumor-infiltrating lymphocytes in response to therapy. To characterize such a T-cell infiltrate, we analyzed the complementarity-determining region 3 (CDR3) of rearranged T-cell receptor (TCR) β chain-coding genes in tumor biopsies obtained before the initiation of BRAFi and 10–14 d later. We observed an increase in the clonality of tumor-infiltrating lymphocytes in 7 of 8 patients receiving BRAFi, with a statistically significant 21% aggregate increase in clonality. Over 80% of individual T-cell clones detected after initiation of BRAFi treatment were new clones. Interestingly, the comparison of tumor infiltrates with clinical responses revealed that patients who had a high proportion of pre-existing dominant clones after the administration of BRAFi responded better to therapy than patients who had a low proportion of such pre-existing dominant clones following BRAFi. These data suggest that although the inhibition of BRAF in melanoma patients results in tumor infiltration by new lymphocytes, the response to treatment appears to be related to the presence of a pre-existing population of tumor-infiltrating T-cell clones. PMID:24251082

An overlap of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis

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Sujit Surendran

2017-01-01

Full Text Available We present a case report of overlap of granulomatosis with polyangiitis (GPA; formerly known as Wegener’s granulomatosis and eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome. We report a 45-year-old female who presented with rapidly progressive renal failure associated with fever, polyarthralgia, and respiratory symptoms with cytoplasmic antineutrophilic cytoplasmic antibody (ANCA and proteinase (PR-3 antigen positivity. Computerized tomography scan of the chest showed diffuse alveolar hemorrhage with renal biopsy revealing pauci-immune necrotizing crescentic glomerulonephritis with intense eosinophilic infiltration suggestive of eosinophilic GPA (EGPA. Our patient had ANCA-associated vasculitis (AAV with features suggestive of both GPA and EGPA. She was treated with methylprednisolone and cyclophosphamide and attained remission after 2 weeks of therapy. This is a rare report of a patient with AAV having features of both EGPA and GPA.

Eosinophilic myositis resulted from Sarcocystis infection in prime marbled beef of Japanese black cattle

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Tohru Kimura

Full Text Available Partial changes of color (greenish to brownish were found in prime marbled beef of Japanese black cattle. The disseminated lesions of the skeletal muscles were histopathologically examined in relation to Sarcocystis infection. The lesions in the muscles showed granulomas with inflammatory cell infiltration. The sarcocysts had a distinct wall, which was radically striated by palisading villar protrusions. The sarcocyst wall was surrounded by degenerative eosinophils and necrotic muscle fibers. In conclusion, eosinophilic myositis in prime marbled beef of Japanese black cattle resulted from Sarcocystis spp. infection. The muscular lesions were characterized by the presence of granulomas and capsulated sarcocysts surrounded by numerous eosinophils. [Vet. World 2011; 4(11.000: 500-502

Eosinophils in biopsy specimens of lichen sclerosus: a not uncommon finding.

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Lester, Elizabeth B; Swick, Brian L

2015-01-01

Evolving lesions of lichen sclerosus (LS) pose a diagnostic challenge owing to an absence of classic findings of epidermal atrophy, dermal sclerosis, a band-like lymphocytic infiltrate and the presence of eosinophils. Retrospective specimens of LS were reviewed. Demographic information, biopsy vs. excision and the following histopathological characteristics were noted: presence and number of eosinophils, epidermal hyperplasia, spongiosis, early/transitional LS, well-developed LS and coexisting squamous cell carcinoma (SCC). Linear regression analysis was performed. The data consisted of 66 biopsies (36 male [M], 30 female [F]), from 53 individuals (33M, 20F), including 57 genital and 9 extragenital biopsies. Seven biopsies showed SCC, 28 showed epidermal hyperplasia and 14 exhibited spongiosis. Thirty-five specimens were early/transitional LS and commonly exhibited epidermal hyperplasia (57%), epidermotropism of lymphocytes (97%) and basement membrane thickening (97%). Thirty-five biopsies (53%) contained eosinophils (23 early/transitional lesions). Male gender (p = 0.074) was associated with increased eosinophils. The presence of SCC (p = 0.014) was a significant predictors of eosinophil number. Epidermal hyperplasia, epidermotropism of lymphocytes and basement membrane thickening are helpful features in identifying early LS. Eosinophils are not an uncommon finding in LS and are most common in male genital lesions and in LS associated with SCC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A possible mechanism in the recruitment of eosinophils and Th2 cells through CD163(+) M2 macrophages in the lesional skin of eosinophilic cellulitis.

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Fujimura, Taku; Kambayashi, Yumi; Furudate, Sadanori; Kakizaki, Aya; Aiba, Setsuya

2014-01-01

M2 macrophages play a critical role in the recruitment of T helper 2 (Th2) regulatory T cells (Treg). To study the role of M2 macrophages and Treg cells in eosinophilic celulitis. We employed immunohistochemical staining for CD163( )and CD206 (macrophages) as well as FoxP3 (Treg), in lesional skin of four cases of eosinophilic cellulitis. CD163(+) CD206(+) M2 macrophages, which were previously reported to produce CCL17 to induce Th2 cells and Treg cells, were predominantly infiltrating the subcutaneous tissues and interstitial area of the dermis. M2 macrophages derived from PBMC showed significantly increased expression of CCL11, CCL17, CCL24 and CCL26 mRNA and production of CCL17 and CCL24, when stimulated by IL-4 or IL- 13. In addition, CCL17-producing cells and CCL24-producing cells were prominent in the lesional skin of EC. Our study sheds light on one of the possible immunological mechanisms of eosinophilic cellulitis.

Esophageal motility in eosinophilic esophagitis.

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Weiss, A H; Iorio, N; Schey, R

2015-01-01

Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus and is a potential cause of dysphagia and food impaction, most commonly affecting young men. Esophageal manometry findings vary from normal motility to aperistalsis, simultaneous contractions, diffuse esophageal spasm, nutcracker esophagus or hypotonic lower esophageal sphincter (LES). It remains unclear whether esophageal dysmotility plays a significant role in the clinical symptoms of EoE. Our aim is to review the pathogenesis, diagnosis, and effect of treatment on esophageal dysmotility in EoE. A literature search utilizing the PubMed database was performed using keywords: eosinophilic esophagitis, esophageal dysmotility, motility, manometry, impedance planimetry, barium esophagogram, endoscopic ultrasound, and dysphagia. Fifteen studies, totaling 387 patients with eosinophilic esophagitis were identified as keeping in accordance with the aim of this study and included in this review. The occurrence of abnormal esophageal manometry was reported to be between 4 and 87% among patients with EoE. Esophageal motility studies have shown reduced distensibility, abnormal peristalsis, and hypotonicity of the LES in patients with EoE, which may also mimic other esophageal motility disorders such as achalasia or nutcracker esophagus. Studies have shown conflicting results regarding the presence of esophageal dysmotility and symptoms with some reports suggesting a higher rate of food impaction, while others report no correlation between motor function and dysphagia. Motility dysfunction of the esophagus in EoE has not been well reported in the literature and studies have reported conflicting evidence regarding the clinical significance of dysmotility seen in EoE. The correlation between esophageal dysmotility and symptoms of EoE remains unclear. Larger studies are needed to investigate the incidence of esophageal dysmotility, clinical implications, and effect of treatment on

A key requirement for CD300f in innate immune responses of eosinophils in colitis.

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Moshkovits, I; Reichman, H; Karo-Atar, D; Rozenberg, P; Zigmond, E; Haberman, Y; Ben Baruch-Morgenstern, N; Lampinen, M; Carlson, M; Itan, M; Denson, L A; Varol, C; Munitz, A

2017-01-01

Eosinophils are traditionally studied in the context of type 2 immune responses. However, recent studies highlight key innate immune functions for eosinophils especially in colonic inflammation. Surprisingly, molecular pathways regulating innate immune activities of eosinophil are largely unknown. We have recently shown that the CD300f is highly expressed by colonic eosinophils. Nonetheless, the role of CD300f in governing innate immune eosinophil activities is ill-defined. RNA sequencing of 162 pediatric Crohn's disease patients revealed upregulation of multiple Cd300 family members, which correlated with the presence of severe ulcerations and inflammation. Increased expression of CD300 family receptors was also observed in active ulcerative colitis (UC) and in mice following induction of experimental colitis. Specifically, the expression of CD300f was dynamically regulated in monocytes and eosinophils. Dextran sodium sulfate (DSS)-treated Cd300f -/- mice exhibit attenuated disease activity and histopathology in comparison with DSS-treated wild type (WT). Decreased disease activity in Cd300f -/- mice was accompanied with reduced inflammatory cell infiltration and nearly abolished production of pro-inflammatory cytokines. Monocyte depletion and chimeric bone marrow transfer experiments revealed a cell-specific requirement for CD300f in innate immune activation of eosinophils. Collectively, we uncover a new pathway regulating innate immune activities of eosinophils, a finding with significant implications in eosinophil-associated gastrointestinal diseases.

GPNMB promotes proliferation of developing eosinophils.

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Hwang, Sae Mi; Kang, Jin Hyun; Kim, Bo Kyum; Uhm, Tae Gi; Kim, Hye Jeong; Lee, Hyune-Hwan; Binas, Bert; Chung, Il Yup

2017-08-01

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane protein that is expressed in a wide variety of cell types, including haematopoietic lineages. We previously demonstrated that GPNMB is one of the most highly expressed genes at an early and intermediate stage of eosinophil development. We herein examined GPNMB expression and its possible functional effect using cord blood (CB) CD34+ haematopoietic stem cells differentiating toward eosinophils during a 24-day culture period. Western blot and confocal microscopy analyses showed that GPNMB reached its highest levels at day 12 with most GPNMB-positive cells also expressing major basic protein 1 (MBP1), an eosinophil granule protein. GPNMB declined thereafter, but was still present at an appreciable level at day 24, the time when CB eosinophils most abundantly expressed MBP1 and were thus considered fully differentiated. When the developing CB cells were cultured in the presence of a blocking anti-GPNMB antibody, cell proliferation was significantly reduced. In agreement, ectopic expression of GPNMB in heterologous cells resulted in a significant increase in cell proliferation, while small interfering RNA of GPNMB inhibited the GPNMB-mediated proliferation. Thus, GPNMB is expressed in a temporal manner during eosinophil development and delivers a proliferative signal upon activation. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Eosinophils from hematopoietic stem cell recipients suppress allogeneic T cell proliferation.

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Andersson, Jennie; Cromvik, Julia; Ingelsten, Madeleine; Lingblom, Christine; Andersson, Kerstin; Johansson, Jan-Erik; Wennerås, Christine

2014-12-01

Eosinophilia has been associated with less severe graft-versus-host disease (GVHD), but the underlying mechanism is unknown. We hypothesized that eosinophils diminish allogeneic T cell activation in patients with chronic GVHD. The capacity of eosinophils derived from healthy subjects and hematopoietic stem cell (HSC) transplant recipients, with or without chronic GVHD, to reduce allogeneic T cell proliferation was evaluated using a mixed leukocyte reaction. Eosinophil-mediated inhibition of proliferation was observed for the eosinophils of both healthy subjects and patients who underwent HSC transplantation. Eosinophils from patients with and without chronic GVHD were equally suppressive. Healthy eosinophils required cell-to-cell contact for their suppressive capacity, which was directed against CD4(+) T cells and CD8(+) T cells. Neither eosinophilic cationic protein, eosinophil-derived neurotoxin, indoleamine 2,3-dioxygenase, or increased numbers of regulatory T cells could account for the suppressive effect of healthy eosinophils. Real-time quantitative PCR analysis revealed significantly increased mRNA levels of the immunoregulatory protein galectin-10 in the eosinophils of both chronic GVHD patients and patients without GVHD, as compared with those from healthy subjects. The upregulation of galectin-10 expression in eosinophils from patients suggests a stimulatory effect of HSC transplantation in itself on eosinophilic galectin-10 expression, regardless of chronic GVHD status. To conclude, eosinophils from HSC transplant recipients and healthy subjects have a T cell suppressive capacity. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Investigation of the roles of fascioliasis and food allergy in intrahepatic eosinophilic proliferative pylephlebitis in Japanese Black cattle.

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Kishida, Kazuki; Ohkusu-Tsukada, Kozo; Hori, Makito; Konnai, Masaki; Abiko, Chieko; Suzuki, Yoshikazu; Yamanome, Yukito; Yoshimura, Hisashi; Michishita, Masaki; Takahashi, Kimimasa

2013-05-01

Intrahepatic eosinophilic proliferative pylephlebitis (EPP) in Japanese Black (JB) cattle generally has been considered to be an atypical form of fascioliasis. However, there are many cases of EPP in which no Fasciola spp. have been detected in the livers of affected cattle. The aims of this study were to ascertain the relationship between EPP and hepatic fascioliasis and to investigate the role of food allergy in the disease. Histologically, EPP lesions were characterised by severe endothelial proliferation of the interlobular veins, accompanied by varying degrees of fibrosis and eosinophilic infiltration in portal areas, which could be differentiated from chronic cholangiohepatitis, the typical lesion of hepatic fascioliasis. In addition to hepatic lesions, all cases of EPP had varying degrees of eosinophilic infiltration in the perilymphoid red pulp of the spleen, whereas both affected and unaffected animals had eosinophilic infiltrates in the mucosa of the small intestine. Antibodies against Fasciola spp. were detected in 1/14 EPP cases by ELISA; the seropositive case had EPP in combination with chronic cholangitis. There was no significant difference in total concentration of IgE between cases of EPP and unaffected cattle. Serum IgE levels specific to curly dock (Rumex crispus) and oats (Avena sativa) were higher in EPP cases than in unaffected cattle by allergen profiling screening testing and ELISA. The results of this study suggest that hepatic fascioliasis is unlikely to be the cause of EPP in JB cattle and that food allergens should be investigated as possible aetiological agents. Copyright © 2012 Elsevier Ltd. All rights reserved.

Eosinophilic Angiocentric Fibrosis of the Nasal Septum

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Yunchuan Li

2013-01-01

Full Text Available Background. Eosinophilic angiocentric fibrosis (EAF is a rare benign condition of unknown aetiology that causes stenosis of the upper respiratory tract. It is most commonly found at the nasal septum and sinus mucosa causing mucosal thickening and nasal obstructive symptoms. The diagnosis is mainly based on characteristic histologic findings. Case Report. A 27-year-old young woman presented with a slow growing mass at her anterior nasal septum for over eight years. She complained of persistent nasal obstruction, epistaxis, sometimes diffused facial pain, and chronic headache. 3 years ago, the tumor was partially resected for ventilation and a nasal septum perforation was left. Imaging findings indicated soft-tissue thickening of the anterior part of septum and adjacent lateral nasal walls. Pathological examination showed numerous inflammatory cells infiltrates containing eosinophils, fibroinflammatory lesion with a whorled appearance fibrosis which typically surrounded vessels. A diagnosis of eosinophilic angiocentric fibrosis was made. All laboratory tests were unremarkable. Skin prick test was positive. The tumor-like lesion was totally resected. Conclusions. EAF is a rare benign and progressive disorder causing destruction. Combined with radiological imaging of EAF historical findings contribute to the diagnosis. It is important to prevent tumor from recurrence by total resection of the lesion.

Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro

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Alves Alessandra C

1997-01-01

Full Text Available In the present study, we have performed a comparative analysis of the effect of selective inhibitors of phosphodiesterase (PDE type III, IV and V on eosinophil chemotaxis triggered by platelet activating factor (PAF and leukotriene B4 (LTB4 in vitro. The effect of the analogues N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt2 cyclic AMP and N2-2'-O- dibutyrylguanosine 3':5' cyclic monophosphate (Bt2 cyclic GMP has also been determined. The eosinophils were obtained from the peritoneal cavity of naive Wistar rats and purified in discontinuous Percoll gradients to 85-95% purity. We observed that pre-incubation of eosinophils with the PDE type IV inhibitor rolipram suppressed the chemotactic response triggered by PAF and LTB4, in association with an increase in the intracellular levels of cyclic AMP. In contrast, neither zaprinast (type V inhibitor nor type III inhibitors milrinone and SK&F 94836 affected the eosinophil migration. Only at the highest concentration tested did the analogue Bt2 cyclic AMP suppress the eosinophil chemotaxis, under conditions where Bt2 cyclic GMP was ineffective. We have concluded that inhibition of PDE IV, but not PDE III or V, was able to block the eosinophil chemotaxis in vitro, suggesting that the suppressive activity of selective PDE IV inhibitors on tissue eosinophil accumulation may, at least, be partially dependent on their ability to directly inhibit the eosinophil migration.

Cyclin-dependent kinase 5 regulates degranulation in human eosinophils.

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Odemuyiwa, Solomon O; Ilarraza, Ramses; Davoine, Francis; Logan, Michael R; Shayeganpour, Anooshirvan; Wu, Yingqi; Majaesic, Carina; Adamko, Darryl J; Moqbel, Redwan; Lacy, Paige

2015-04-01

Degranulation from eosinophils in response to secretagogue stimulation is a regulated process that involves exocytosis of granule proteins through specific signalling pathways. One potential pathway is dependent on cyclin-dependent kinase 5 (Cdk5) and its effector molecules, p35 and p39, which play a central role in neuronal cell exocytosis by phosphorylating Munc18, a regulator of SNARE binding. Emerging evidence suggests a role for Cdk5 in exocytosis in immune cells, although its role in eosinophils is not known. We sought to examine the expression of Cdk5 and its activators in human eosinophils, and to assess the role of Cdk5 in eosinophil degranulation. We used freshly isolated human eosinophils and analysed the expression of Cdk5, p35, p39 and Munc18c by Western blot, RT-PCR, flow cytometry and immunoprecipitation. Cdk5 kinase activity was determined following eosinophil activation. Cdk5 inhibitors were used (roscovitine, AT7519 and small interfering RNA) to determine its role in eosinophil peroxidase (EPX) secretion. Cdk5 was expressed in association with Munc18c, p35 and p39, and phosphorylated following human eosinophil activation with eotaxin/CCL11, platelet-activating factor, and secretory IgA-Sepharose. Cdk5 inhibitors (roscovitine, AT7519) reduced EPX release when cells were stimulated by PMA or secretory IgA. In assays using small interfering RNA knock-down of Cdk5 expression in human eosinophils, we observed inhibition of EPX release. Our findings suggest that in activated eosinophils, Cdk5 is phosphorylated and binds to Munc18c, resulting in Munc18c release from syntaxin-4, allowing SNARE binding and vesicle fusion, with subsequent eosinophil degranulation. Our work identifies a novel role for Cdk5 in eosinophil mediator release by agonist-induced degranulation. © 2014 John Wiley & Sons Ltd.

Role of Endoscopy in Diagnosis and Management of Pediatric Eosinophilic Esophagitis.

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Muir, Amanda B; Merves, Jamie; Liacouras, Chris A

2016-01-01

Eosinophilic esophagitis (EoE) is a chronic allergic (immune-mediated) disease that leads to esophageal dysfunction and feeding disorders in children. Foods, and possibly environmental triggers, cause an inflammatory response in the esophagus, leading to esophageal inflammation, eosinophilic infiltration, and esophageal dysmotility, which may progress to dysphagia, food impaction, and esophageal stricture. Endoscopy with biopsy and histologic evaluation is currently the only method to diagnose EoE. Once diagnosed with EoE, children undergo follow-up endoscopy after therapy initiation and adjustments to ensure remission. Furthermore, children with food impactions or strictures may require endoscopic intervention such as foreign body removal and/or esophageal dilation. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of AN Eosinophil Specific Monoclonal Antibody in Assessing Eosinophil Function.

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Minkoff, Marjorie Sue

A monoclonal antibody to an eosinophil specific determinant is very important in assessing eosinophil function during helminthic infection. Eosinophils induced by Schistosoma mansoni infection in BALB/c mice were used to induce C57B1/6 immunocytes for production of hybridomas secreting eosinophil monoclonal antibodies. These antibodies were shown to react with an eosinophil surface epitope but not with neutrophils or macrophages as determined by ELISA, immunodiffusion, immunofluorescence, and immunoblot assay. Affinity chromatography with eosinophil chemotactic factor-sepharose consistently selected out a { rm M_ R} 67,000 protein from solubilized eosinophil membrane antigens but not from neutrophil and macrophage antigens. In vitro studies showed that the eosinophil-specific monoclonal antibodies abrogated antibody-dependent eosinophil -mediated killing of S. mansoni schistosomula using mouse, rat or human eosinophils. Neutrophil and macrophage killing activities were unaffected. The monoclonal antibodies effected complement-dependent lysis of mouse and rat eosinophils but not of human eosinophils. ECF-treated eosinophils showed enhanced killing of schistosomula which was blocked by the monoclonal antibody. Murine and human eosinophils preincubated with monoclonal antibody exhibited decreased chemotaxis to ECF at optimal chemotactic concentrations. The monoclonal antibody also blocked eosinophil binding to ECF- sepharose beads. In vivo induction of peripheral blood eosinophilia by injection of S. mansoni eggs was suppressed by injections of monoclonal antibodies 2CD13 and 2QD45 in mouse and rat experimental models. Eosinophilia induced by keyhole limpet hemocyanin- cyclophosphamide treatment was also suppressed by monoclonal antibody in both murine and rat systems. Pulmonary granulomas in mice given egg injection and monoclonal antibody were smaller and contained fewer eosinophils than those granulomas from mice given eggs only. In immuno-biochemical studies, the

Dasatinib inhibits the growth and survival of neoplastic human eosinophils (EOL-1) through targeting of FIP1L1-PDGFRalpha.

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Baumgartner, Christian; Gleixner, Karoline V; Peter, Barbara; Ferenc, Veronika; Gruze, Alexander; Remsing Rix, Lily L; Bennett, Keiryn L; Samorapoompichit, Puchit; Lee, Francis Y; Pickl, Winfried F; Esterbauer, Harald; Sillaber, Christian; Superti-Furga, Giulio; Valent, Peter

2008-10-01

Chronic eosinophilic leukemia (CEL) is a myeloproliferative disorder characterized by molecular and/or cytogenetic evidence of clonality of eosinophils, marked eosinophilia, and organ damage. In many patients, the transforming mutation FIP1L1-PDGFRalpha and the related CHIC2 deletion are found. The respective oncoprotein, FIP1L1-PDGFRalpha, is considered to play a major role in malignant cell growth in CEL. The tyrosine kinase (TK) inhibitor imatinib (STI571) has been described to counteract the TK activity of FIP1L1-PDGFRalpha in most patients. However, not all patients with CEL show a response to imatinib. Therefore, several attempts have been made to identify other TK inhibitors that counteract growth of neoplastic eosinophils. We provide evidence that dasatinib, a multi-targeted kinase inhibitor, blocks the growth and survival of EOL-1, an eosinophil leukemia cell line carrying FIP1L1-PDGFRalpha. The effects of dasatinib on proliferation of EOL-1 cells were dose-dependent, with an IC50 of 0.5 to 1 nM, which was found to be in the same range when compared to IC50 values produced with imatinib. Dasatinib was also found to induce apoptosis in EOL-1 cells in a dose-dependent manner (IC50: 1-10 nM). The apoptosis-inducing effects of dasatinib on EOL-1 cells were demonstrable by light microscopy, flow cytometry, and in a TUNEL assay. In Western blot experiments, dasatinib completely blocked the phosphorylation of FIP1L1-PDGFRalpha in EOL-1 cells. Dasatinib inhibits the growth of leukemic eosinophils through targeting of the disease-related oncoprotein FIP1L1-PDGFRalpha. Based on this observation, dasatinib may be considered as a new interesting treatment option for patients with CEL.

Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation.

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Shirin Elhaik Goldman

Full Text Available The function of NCR1 was studied in a model of experimental asthma, classified as a type 1 hypersensitivity reaction, in mice. IgE levels were significantly increased in the serum of OVA immunized NCR1 deficient (NCR1gfp/gfp mice in comparison to OVA immunized wild type (NCR1+/+ and adjuvant immunized mice. Histological analysis of OVA immunized NCR1gfp/gfp mice revealed no preservation of the lung structure and overwhelming peribronchial and perivascular granulocytes together with mononuclear cells infiltration. OVA immunized NCR+/+ mice demonstrated preserved lung structure and peribronchial and perivascular immune cell infiltration to a lower extent than that in NCR1gfp/gfp mice. Adjuvant immunized mice demonstrated lung structure preservation and no immune cell infiltration. OVA immunization caused an increase in PAS production independently of NCR1 presence. Bronchoalveolar lavage (BAL revealed NCR1 dependent decreased percentages of eosinophils and increased percentages of lymphocytes and macrophages following OVA immunization. In the OVA immunized NCR1gfp/gfp mice the protein levels of eosinophils' (CCL24 and Th2 CD4+ T-cells' chemoattractants (CCL17, and CCL24 in the BAL are increased in comparison with OVA immunized NCR+/+ mice. In the presence of NCR1, OVA immunization caused an increase in NK cells numbers and decreased NCR1 ligand expression on CD11c+GR1+ cells and decreased NCR1 mRNA expression in the BAL. OVA immunization resulted in significantly increased IL-13, IL-4 and CCL17 mRNA expression in NCR1+/+ and NCR1gfp/gfp mice. IL-17 and TNFα expression increased only in OVA-immunized NCR1+/+mice. IL-6 mRNA increased only in OVA immunized NCR1gfp/gfp mice. Collectively, it is demonstrated that NCR1 dampens allergic eosinophilic airway inflammation.

An atypical presentation of cardiac tamponade and periorbital swelling in a patient with eosinophilic granulomatosis with polyangiitis: a case report.

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Keefe, Alexandra C; Hymas, Joseph C; Emerson, Lyska L; Ryan, John J

2017-09-24

Eosinophilic granulomatosis with polyangiitis is a rare, necrotizing systemic vasculitis associated with asthma and hypereosinophilia. Its cause and pathophysiology are still being elucidated. We report a case of eosinophilic granulomatosis with polyangiitis in a 50-year-old Caucasian woman who presented with chest pain, dyspnea at rest, fever, and periorbital swelling. She was found to have significant hypereosinophilia and cardiac tamponade physiology. A biopsy confirmed extensive infiltration of both lungs and pericardium by eosinophils. She did not have any anti-neutrophil cytoplasmic antibodies. Eosinophilic granulomatosis with polyangiitis diagnosis does not require the presence of anti-neutrophil cytoplasmic antibodies. Anti-neutrophil cytoplasmic antibody-positive and anti-neutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis may present with different clinical phenotypes, perhaps suggesting two distinct disease etiologies and distinct pathophysiology.

Eosinophil Resistance to Glucocorticoid-Induced Apoptosis is Mediated by the Transcription Factor NFIL3

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Pazdrak, Konrad; Moon, Young; Straub, Christof; Stafford, Susan; Kurosky, Alexander

2016-01-01

The mainstay of asthma therapy, glucocorticoids (GCs) exert their therapeutic effects through the inhibition of inflammatory signaling and induction of eosinophil apoptosis. However, laboratory and clinical observations of GC-resistant asthma suggest that GCs' effects on eosinophil viability may depend on the state of eosinophil activation. In the present study we demonstrate that eosinophils stimulated with IL-5 show impaired prop-aptoptotic response to GCs. We sought to determine the contribution of GC-mediated transactivating (TA) and transrepressing (TR) pathways in modulation of activated eosinophils' response to GC by comparing their response to the selective GC receptor (GR) agonist Compound A (CpdA) devoid of TA activity to that upon treatment with Dexamethasone (Dex). IL-5-activated eosinophils showed contrasting responses to CpdA and Dex, as IL-5-treated eosinophils showed no increase in apoptosis compared to cells treated with Dex alone, while CpdA elicited an apoptotic response regardless of IL-5 stimulation. Proteomic analysis revealed that both Nuclear Factor IL-3 (NFIL3) and Map Kinase Phosphatase 1 (MKP1) were inducible by IL-5 and enhanced by Dex; however, CpdA had no effect on NFIL3 and MKP1 expression. We found that inhibiting NFIL3 with specific siRNA or by blocking the IL-5-inducible Pim-1 kinase abrogated the protective effect of IL-5 on Dex-induced apoptosis, indicating crosstalk between IL-5 anti-apoptotic pathways and GR-mediated TA signaling occurring via the NFIL3 molecule. Collectively, these results indicate that 1) GCs' TA pathway may support eosinophil viability in IL-5-stimulated cells through synergistic upregulation of NFIL3; and 2) functional inhibition of IL-5 signaling (anti-Pim1) or the use of selective GR agonists that don't upregulate NFIL3 may be effective strategies for the restoring pro-apoptotic effect of GCs on IL-5-activated eosinophils. PMID:26880402

Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis

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Griseri, Thibault; Arnold, Isabelle C.; Pearson, Claire; Krausgruber, Thomas; Schiering, Chris; Franchini, Fanny; Schulthess, Julie; McKenzie, Brent S.; Crocker, Paul R.; Powrie, Fiona

2015-01-01

Summary The role of intestinal eosinophils in immune homeostasis is enigmatic and the molecular signals that drive them from protective to tissue damaging are unknown. Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal inflammation was characterized by increased bone marrow eosinopoiesis and accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil depletion ameliorated colitis, implicating eosinophils in disease pathogenesis. GM-CSF was a potent activator of eosinophil effector functions and intestinal accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast neutrophil accumulation was GM-CSF independent and dispensable for colitis. In addition to TNF secretion, release of eosinophil peroxidase promoted colitis identifying direct tissue-toxic mechanisms. Thus, eosinophils are key perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic target. PMID:26200014

Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

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Konno, Yasunori; Ueki, Shigeharu; Takeda, Masahide; Kobayashi, Yoshiki; Tamaki, Mami; Moritoki, Yuki; Oyamada, Hajime; Itoga, Masamichi; Kayaba, Hiroyuki; Omokawa, Ayumi; Hirokawa, Makoto

2015-01-01

Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

Identification of JAK2 as a mediator of FIP1L1-PDGFRA-induced eosinophil growth and function in CEL.

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Bin Li

Full Text Available The Fip1-like1 (FIP1L1-platelet-derived growth factor receptor alpha fusion gene (F/P arising in the pluripotent hematopoietic stem cell (HSC,causes 14% to 60% of patients with hypereosinophilia syndrome (HES. These patients, classified as having F/P (+ chronic eosinophilic leukemia (CEL, present with clonal eosinophilia and display a more aggressive disease phenotype than patients with F/P (- HES patients. The mechanisms underlying predominant eosinophil lineage targeting and the cytotoxicity of eosinophils in this leukemia remain unclear. Given that the Janus tyrosine kinase (JAK/signal transducers and activators of transcription (Stat signaling pathway is key to cytokine receptor-mediated eosinophil development and activated Stat3 and Stat5 regulate the expression of genes involved in F/P malignant transformation, we investigated whether and how JAK proteins were involved in the pathogenesis of F/P-induced CEL. F/P activation of JAK2, Stat3 and Stat5, were confirmed in all the 11 F/P (+ CEL patients examined. In vitro inhibition of JAK2 in EOL-1, primary F/P(+ CEL cells (PC and T674I F/P Imatinib resistant cells(IR by either JAK2-specific short interfering RNA (siRNA or the tryphostin derivative AG490(AG490, significantly reduced cellular proliferation and induced cellular apoptosis. The F/P can enhance the IL-5-induced JAK2 activation, and further results indicated that JAK2 inhibition blocked IL-5-induced cellular migration and activation of the EOL-1 and PC cells in vitro. F/P-stimulation of the JAK2 suppressed cells led to a significantly reduction in Stat3 activation, but relatively normal induction of Stat5 activation. Interestingly, JAK2 inhibition also reduced PI3K, Akt and NF-κB activity in a dose-dependent manner, and suppressed expression levels of c-Myc and Survivin. These results strongly suggest that JAK2 is activated by F/P and is required for F/P stimulation of cellular proliferation and infiltration, possibly through

Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1-PDGFRα

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Ishihara, Kenji; Kitamura, Hajime; Hiraizumi, Kenji; Kaneko, Motoko; Takahashi, Aki; Zee, OkPyo; Seyama, Toshio; Hong, JangJa; Ohuchi, Kazuo; Hirasawa, Noriyasu

2008-01-01

The constitutively activated tyrosine kinase Fip1-like 1 (FIP1L1)-platelet-derived growth factor receptor α (PDGFRα) causes eosinophilic leukemia EoL-1 cells to proliferate. Recently, we demonstrated that histone deacetylase inhibitors suppressed this proliferation and induced the differentiation of EoL-1 cells into eosinophils in parallel with a decrease in the level of FIP1L1-PDGFRα. In this study, we analyzed the mechanism by which FIP1L1-PDGFRα induces the proliferation and whether the suppression of cell proliferation triggers the differentiation into eosinophils. The FIP1L1-PDGFRα inhibitor imatinib inhibited the proliferation of EoL-1 cells and decreased the level of the oncoprotein c-Myc as well as the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK). The proliferation of EoL-1 cells and expression of c-Myc were also inhibited by the MEK inhibitor U0126 and JNK inhibitor SP600125. The expression of the eosinophilic differentiation marker CCR3 was not induced by imatinib. These findings suggest that FIP1L1-PDGFRα induces the proliferation of EoL-1 cells through the induction of c-Myc expression via ERK and JNK signaling pathways, but is not involved in the inhibition of differentiation toward mature eosinophils

T-helper 2 cytokines, transforming growth factor β1, and eosinophil products induce fibrogenesis and alter muscle motility in patients with eosinophilic esophagitis.

Science.gov (United States)

Rieder, Florian; Nonevski, Ilche; Ma, Jie; Ouyang, Zhufeng; West, Gail; Protheroe, Cheryl; DePetris, Giovanni; Schirbel, Anja; Lapinski, James; Goldblum, John; Bonfield, Tracey; Lopez, Rocio; Harnett, Karen; Lee, James; Hirano, Ikuo; Falk, Gary; Biancani, Piero; Fiocchi, Claudio

2014-05-01

Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEFs), human esophageal muscle cells (HEMCs), and esophageal muscle strips to eosinophil-derived products. Biopsy specimens were collected via endoscopy from the upper, middle, and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls). Primary cultures of esophageal fibroblasts and muscle cells were derived from 12 freshly resected human esophagectomy specimens. Eosinophil distribution was investigated by histologic analyses of full-thickness esophageal tissue. Active secretion of EoE-related mediators was assessed from medium underlying mucosal biopsy cultures. We quantified production of fibronectin and collagen I by HEF and HEMC in response to eosinophil products. We also measured the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by, and adhesion of human eosinophils to, HEFs and HEMCs. Eosinophil products were tested in an esophageal muscle contraction assay. Activated eosinophils were present in all esophageal layers. Significantly higher concentrations of eosinophil-related mediators were secreted spontaneously in mucosal biopsy specimens from patients with EoE than controls. Exposure of HEFs and HEMCs to increasing concentrations of eosinophil products or co-culture with eosinophils caused HEFs and HEMCs to increase secretion of fibronectin and collagen I; this was inhibited by blocking transforming growth factor β1 and p38 mitogen-activated protein kinase signaling. Eosinophil binding to HEFs and HEMCs increased after incubation of mesenchymal cells with eosinophil-derived products, and decreased after blockade of transforming growth factor β1 and p38 mitogen-activated protein kinase blockade. Eosinophil products reduced

A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst

DEFF Research Database (Denmark)

Royer, J F; Schratl, P; Lorenz, S

2007-01-01

developed small molecule antagonist of CRTH2, Cay10471, on eosinophil function with respect to recruitment, respiratory burst and degranulation. METHODS: Chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils were determined using microBoyden chambers. Eosinophil release...... from bone marrow was investigated in the in situ perfused guinea pig hind limb preparation. Respiratory burst and degranulation were measured by flow cytometry. RESULTS: Cay10471 bound with high affinity to recombinant human and guinea pig CRTH2, but not DP, receptors. The antagonist prevented the PGD......(2)-induced release of eosinophils from guinea pig bone marrow, and inhibited the chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils. Pretreatment with PGD(2) primed eosinophils for chemotaxis towards eotaxin, and this effect was prevented by Cay10471. In contrast...

Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs.

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Wicher, Sarah A; Jacoby, David B; Fryer, Allison D

2017-06-01

Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals. Copyright �

GS143, an IκB ubiquitination inhibitor, inhibits allergic airway inflammation in mice

International Nuclear Information System (INIS)

Hirose, Koichi; Wakashin, Hidefumi; Oki, Mie; Kagami, Shin-ichiro; Suto, Akira; Ikeda, Kei; Watanabe, Norihiko; Iwamoto, Itsuo; Furuichi, Yasuhiro; Nakajima, Hiroshi

2008-01-01

Asthma is characterized by airway inflammation with intense eosinophil infiltration and mucus hyper-production, in which antigen-specific Th2 cells play critical roles. Nuclear factor-κB (NF-κB) pathway has been demonstrated to be essential for the production of Th2 cytokines and chemokines in the airways in murine asthma models. In the present study, we examined the effect of GS143, a novel small-molecule inhibitor of IκB ubiquitination, on antigen-induced airway inflammation and Th2 cytokine production in mice. Intranasal administration of GS143 prior to antigen challenge suppressed antigen-induced NF-κB activation in the lung of sensitized mice. Intranasal administration of GS143 also inhibited antigen-induced eosinophil and lymphocyte recruitment into the airways as well as the expression of Th2 cytokines and eotaxin in the airways. Moreover, GS143 inhibited antigen-induced differentiation of Th2 cells but not of Th1 cells in vitro. Taken together, these results suggest that IκB ubiquitination inhibitor may have therapeutic potential against asthma

The effect of hepatocyte growth factor on secretory functions in human eosinophils.

Science.gov (United States)

Yamauchi, Yumiko; Ueki, Shigeharu; Konno, Yasunori; Ito, Wataru; Takeda, Masahide; Nakamura, Yuka; Nishikawa, Junko; Moritoki, Yuki; Omokawa, Ayumi; Saga, Tomoo; Hirokawa, Makoto

2016-12-01

Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro-fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study. We found that HGF significantly inhibited IL-5-induced secretion of TGF-β and VEGF from human eosinophils. The inhibitory effect is not associated with TGF-β transcription; rather, it is associated with ultrastructural granule emptying and loss of intracellular TGF-β contents, indicating HGF inhibits the process of piecemeal degranulation. The effect of HGF on extracellular trap cell death (ETosis) that mediates cytolytic degranulation was also investigated; however, immobilized IgG- or phorbol myristate acetate-induced ETosis was only minimally attenuated by HGF. These results reveal the effect of HGF on the distinct pathways of eosinophil secretory functions and also provide novel insights into the role of HGF in the pathogenesis of allergic inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced activation of eosinophils in peripheral blood and implications for eosinophilic esophagitis diagnosis.

Science.gov (United States)

Botan, Valéria; Dos Santos Borges, Tatiana Karla; Rocha Alves, Érica Alessandra; Claudino Pereira Couto, Shirley; Bender Kohnert Seidler, Heinrich; Muniz-Junqueira, Maria Imaculada

2017-07-01

Eosinophils are markers of the eosinophilic esophagitis (EoE) disease, and this work aimed to assess whether activation of eosinophils could be a noninvasive test to contribute for EoE diagnosis. The activation state of peripheral blood eosinophils in EoE patients and control subjects was assessed based on the morphological aspects of the eosinophil after adherence to slide. Cyclooxygenase-2 and 5-lipoxygenase expressions were evaluated by means of immunofluorescence microscopy to verify if and which eicosanoid pathway is triggered in eosinophils in blood in EoE. The eosinophils of patients with EoE were significantly more activated than those of control individuals. The lowest percentage of normal eosinophils for control subjects was 40%, while the highest percentage of eosinophils of normal aspect for patients with EoE was 32%. Considering 36% as a cutoff for normal eosinophils, this value differentiated all individuals with EoE from individuals without the disease with a sensitivity of 100%, considering the diagnosis of EoE as currently defined. Eosinophils of EoE patients showed higher expression of cyclooxygenase-2 than those of control subjects. The quantification of morphological changes in eosinophils is a feasible, easy, and reliable manner to identify EoE patients. Therefore, patients with symptoms of esophageal dysfunction showing higher than 36% activated eosinophils in peripheral blood could be a useful way to help definition and diagnostic criterion for EoE. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome as a differential diagnosis of hypereosinophilic syndromes

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Yuri Albuquerque Pessoa Santos

2017-01-01

Full Text Available Eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome, is a rare systemic disease situated between primary small vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCAs and hypereosinophilic syndromes (HES. Here, we present a case of EGPA in a 38-year-old male, with a previous diagnosis of asthma, who presented with fever, migratory lung infiltrates and systemic eosinophilia that was refractory to previous courses of antibiotics. This case highlights the importance of the primary care physician understanding the differential diagnosis of pulmonary eosinophilic syndromes.

Expression of cysLT1 and cysLT2 Receptor in Chronic Hyperplastic Eosinophilic Sinusitis

International Nuclear Information System (INIS)

Ouyang, Yuhui; Kamijo, Atsushi; Murata, Shin-ichi; Okamoto, Atsushi; Endo, Shuichiro; Katoh, Ryohei; Masuyama, Keisuke

2009-01-01

Elevated production of cysteinyl leukotrienes (cysLTs) from sinus tissues and abundant sinus eosinophils are characteristic features of chronic hyperplastic eosinophilic sinusitis (CHS). CysLTs exert their action through G-protein-coupled receptors named cysLTs receptor type I (cysLT1R) and type II (cysLT2R). These expressions of cysLT receptors in the sinus mucosa have yet to be clarified and the relationship between eosinophilia and the expression of these receptors remains obscure. We compared the expressions of cysLT1R and cysLT2R in the sinus mucosa in patients with CHS, non-eosinophilic chronic sinusitis (NECS), and control sinus tissues; and analyzed the correlation between the expression of CysLTRs and the presence of sinus eosinophils by immunohistochemistry and real-time PCR. A significantly higher percentage of eosinophils expressing cysLT2R protein was observed in patients with CHS compared with NECS and controls. In addition, cysLT2R mRNA expression in CHS was significantly higher than in NECS and controls. Furthermore, a positive correlation was observed between cysLT2R mRNA expression and the number of infiltrated eosinophils. In contrast, the cysLT1R mRNA expression did not differ significantly among these groups. The effect of cysLTs on sinus eosinophils may be mediated through the cysLT2R in patients with CHS. These results may suggest the therapeutic benefit of cysLT2R antagonists in CHS

Eosinophil autofluorescence and its use in isolation and analysis of human eosinophils using flow microfluorometry

International Nuclear Information System (INIS)

Weil, G.J.; Chused, T.M.

1981-01-01

Unstained human eosinophils exhibit unusually bright autofluorescence, which allows them to be distinguished from other leukocytes using fluorescence microscopy. Eosinophil fluorescence is associated with the cytoplasmic granules of the cells. Eosinophil granule extracts, containing an as-yet-undefined eosinophil fluorescence factor, exhibited excitation maxima at 370 nm and 450 nm, with maximum emission at 520 nm. Eosinophils adhering to opsonized parasites in vitro deposit fluorescent material onto the parasite surface. Eosinophil fluorescence was of sufficient intensity to allow the preparation of viable, highly enriched (greater than or equal to 98%), eosinophil suspensions from peripheral blood of normal and eosinophilic donors using a fluorescence-activated cell sorter. Quantitative studies of eosinophil autofluorescence were performed using flow microfluorometry. Fluorescence intensity of blood eosinophils from normal volunteers and eosinophilic patients varied inversely with the log of the donor's absolute eosinophil count regardless of clinical diagnosis

Inhibition of PAF-induced expression of CD11b and shedding of L-selectin on human neutrophils and eosinophils by the type IV selective PDE inhibitor, rolipram

NARCIS (Netherlands)

Dijkhuizen, B; deMonchy, JGR; Dubois, AEJ; Gerritsen, J; Kauffman, HF

We quantitatively determined whether the selective phosphodiesterase (PDE) inhibitor, rolipram, inhibits changes in the adhesion molecules CD11b and L-selectin on platelet-activating factor (PAF)-stimulated human neutrophils and eosinophils in vitro. Incubations were performed in human whole blood

Eosinophils in Autoimmune Diseases

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Daniela Čiháková

2017-04-01

Full Text Available Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

Eosinophils in Autoimmune Diseases

Science.gov (United States)

Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

2017-01-01

Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

Proteomics of Eosinophil Activation

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Deane F. Mosher

2017-09-01

Full Text Available We recently identified and quantified >7,000 proteins in non-activated human peripheral blood eosinophils using liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS and described phosphoproteomic changes that accompany acute activation of eosinophils by interleukin-5 (IL5 (1. These data comprise a treasure trove of information about eosinophils. We illustrate the power of label-free LC–MS/MS quantification by considering four examples: complexity of eosinophil STATs, contribution of immunoproteasome subunits to eosinophil proteasomes, complement of integrin subunits, and contribution of platelet proteins originating from platelet–eosinophil complexes to the overall proteome. We describe how isobaric labeling enables robust sample-to-sample comparisons and relate the 220 phosphosites that changed significantly upon treatment with IL5 to previous studies of eosinophil activation. Finally, we review previous attempts to leverage the power of mass spectrometry to discern differences between eosinophils of healthy subjects and those with eosinophil-associated conditions and point out features of label-free quantification and isobaric labeling that are important in planning future mass spectrometric studies.

Modulation of eosinophil generation and migration by Mangifera indica L. extract (Vimang).

Science.gov (United States)

Sá-Nunes, Anderson; Rogerio, Alexandre P; Medeiros, Alexandra I; Fabris, Viciany E; Andreu, Gilberto P; Rivera, Dagmar G; Delgado, René; Faccioli, Lúcia H

2006-09-01

The effects of Vimang, an aqueous extract of the stem bark of Mangifera indica L. (Anacardiaceae), on cell migration in an experimental model of asthma was investigated. In vivo treatment of Toxocara canis-infected BALB/c mice for 18 days with 50 mg/kg Vimang reduced eosinophil migration into the bronchoalveolar space and peritoneal cavity. Also, eosinophil generation in bone marrow and blood eosinophilia were inhibited in infected mice treated with Vimang. This reduction was associated with inhibition of IL-5 production in serum and eotaxin in lung homogenates. In all these cases the effects of Vimang were more selective than those observed with dexamethasone. Moreover, Vimang treatment is not toxic for the animals, as demonstrated by the normal body weight increase during infection. These data confirm the potent anti-inflammatory effect of Vimang and support its potential use as an alternative therapeutic drug to the treatment of eosinophilic disorders including those caused by nematodes and allergic diseases.

Eosinophilic Mucin Otomastoiditis and Otopolyposis: A Progressive Form of Eosinophilic Otitis Media.

Science.gov (United States)

Azadarmaki, Roya; Westra, William; Prasad, Sanjay

2015-09-01

The purpose of this study is to introduce and define a disease entity on a continuum of eosinophilic otitis media: eosinophilic mucin otomastoiditis and otopolyposis. A case of a 66-year-old woman with complicated chronic otitis media is reported. A literature review of the National Library of Medicine's online database, with a focus on eosinophilic otitis media and eosinophilic mucin rhinosinusitis, was performed. The authors report the case of a 66-year-old woman with a history of asthma, chronic rhinosinusitis, nasal polyposis, and chronic otitis media who presented with allergic middle ear mucin and otic polyps. Treatment involved a tympanomastoidectomy with removal of otic polyps and steroid therapy. Eosinophilic mucin otomastoiditis with otopolyposis is a disease entity on a continuum of eosinophilic otitis media. This disease process shares similarities with eosinophilic mucin rhinosinusitis. Otic polypectomy and steroids are suggested therapeutic measures. © The Author(s) 2015.

Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition.

Science.gov (United States)

Osada, Takuya; Morse, Michael A; Hobeika, Amy; Diniz, Marcio A; Gwin, William R; Hartman, Zachary; Wei, Junping; Guo, Hongtao; Yang, Xiao-Yi; Liu, Cong-Xiao; Kaneko, Kensuke; Broadwater, Gloria; Lyerly, H Kim

2017-01-01

Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions. Both preventative and therapeutic Ad-HER3-FL immunization delayed tumor growth but were associated with both intratumoral PD-1 expressing CD8 + T cells and regulatory CD4 + T cell infiltrates. Immune checkpoint inhibition with either anti-PD-1 or anti-PD-L1 antibodies increased intratumoral CD8 + T cell infiltration and eliminated tumor following preventive vaccination with Ad-HER3-FL vaccine. The combination of dual PD-1/PD-L1 and CTLA4 blockade slowed the growth of tumor in response to Ad-HER3-FL in the therapeutic model. We conclude that HER3-targeting vaccines activate HER3-specific T cells and induce anti-HER3 specific antibodies, which alters the intratumoral T cell infiltrate and responses to immune checkpoint inhibition.

Eosinophils from eosinophilic oesophagitis patients have T cell suppressive capacity and express FOXP3.

Science.gov (United States)

Lingblom, C; Wallander, J; Ingelsten, M; Bergquist, H; Bove, M; Saalman, R; Welin, A; Wennerås, C

2017-03-01

Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (T regs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of T regs , was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in T regs . To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE. © 2016 British Society for Immunology.

Gene-specific sex effects on eosinophil infiltration in leishmaniasis

Czech Academy of Sciences Publication Activity Database

Slapničková, Martina; Volkova, Valeriya; Čepičková, Marie; Kobets, Tetyana; Šíma, Matyáš; Svobodová, M.; Demant, P.; Lipoldová, Marie

2016-01-01

Roč. 7, podzim (2016), č. článku 59. ISSN 2042-6410 R&D Projects: GA ČR(CZ) GA14-30186S; GA ČR GP13-41002P; GA MŠk LH12049; GA ČR GA16-22346S Institutional support: RVO:68378050 Keywords : Leishmania major * Mouse model * Eosinophii infiltration * Genetic control * QTL * Sex influence Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.635, year: 2016

Eosinophils.

Science.gov (United States)

Radonjic-Hösli, Susanne; Simon, Hans-Uwe

2014-01-01

In 1846, T. Wharton-Jones described a coarsely granular stage in the development of granulocytic cells in animal and human blood. Shortly thereafter, Max Schultze redefined the coarsely granular cells as a type distinct from finely granular cells, rather than just a developmental stage. It was, however, not until 1879, when Paul Ehrlich introduced a method to distinguish granular cells by the staining properties of their granules, that a classification became possible. An intensive staining for eosin, among other aniline dyes, was eponymous for the coarsely granular cell type, which thereupon became referred to as eosinophil granulocyte. Eosinophilia had already been described in many diseases by the late 19th century. The role of these cells, however, today remains a matter of continuing speculation and investigation. Many functions have been attributed to the eosinophil over the years, often linked to increasing knowledge about the granular and cytoplasmatic contents. A better understanding of the regulatory mechanisms of eosinopoiesis has led to the development of knock-out mice strains as well as therapeutic strategies for reducing the eosinophil load in patients. The effect of these therapeutics and the characterization of the knock-out phenotypes have led to a great increase in the knowledge of the role of the eosinophil in disease. Today we think of the eosinophil as a multifunctional cell involved in host defense, tissue damage and remodeling, as well as immunomodulation. © 2014 S. Karger AG, Basel.

Sinusitis with eosinophilic otitis media

International Nuclear Information System (INIS)

Kawano, Toshiro; Ishitoya, Junichi; Tsukuda, Mamoru

2007-01-01

Eosinophilic otitis media is an intractable inflammation of the middle ear combined with bronchial asthma. According to a national epidemiological investigation on eosinophilic otitis media, it is assumed that eosinophilic otitis media are combined with sinusitis in about 74% of their cases. On the other hand, organizational images of eosinophilic otitis media and eosinophilic sinusitis are similar, and steroid therapy is effective together, and it is thought that they are involved in the idea of one airway one disease, but the details of sinusitis combined with the eosinophilic otitis media are unidentified. Therefore, we examined the kinds of the sinusitis combined with eosinophilic otitis media. We diagnosed 18 cases (male: 2 cases, female: 16 cases) (average age: 54.6 years old) as eosinophilic otitis media according to the diagnostic criteria. And, by the CT views of a paranasal sinus, blood tests, existence of the nasal polyp, etc, we investigated the kinds of sinusitis combined with eosinophilic otitis media. It turned out that bronchial asthma was combined with eosinophilic otitis media in 17 of 18 cases (airway hypersensitivity did sthenia of one case, but the asthma did not yet developed), and 6 cases were combined with aspirin induced asthma (AIA), and 3 cases were combined with Churg-Strauss syndromes (CSS). 10 case (55.6%) of 17 eosinophilic otitis media were combined with eosinophilic sinusitis. And 4 cases (22.2%) of 17 eosinophilic otitis media were combined with chronic sinusitis, 4 cases (22.2%) of 17 eosinophilic otitis media were not combined with sinusitis. We concluded that eosinophilic otitis media was not always combined with eosinophilic sinusitis. The idea of one airway one disease was not applied to this examination. (author)

Sinusitis with eosinophilic otitis media

Energy Technology Data Exchange (ETDEWEB)

Kawano, Toshiro; Ishitoya, Junichi [Yokohama City Univ., Medical Center, Yokohama, Kanagawa (Japan); Tsukuda, Mamoru [Yokohama City Univ., Graduate School of Medicine, Yokohama, Kanagawa (Japan)

2007-09-15

Eosinophilic otitis media is an intractable inflammation of the middle ear combined with bronchial asthma. According to a national epidemiological investigation on eosinophilic otitis media, it is assumed that eosinophilic otitis media are combined with sinusitis in about 74% of their cases. On the other hand, organizational images of eosinophilic otitis media and eosinophilic sinusitis are similar, and steroid therapy is effective together, and it is thought that they are involved in the idea of one airway one disease, but the details of sinusitis combined with the eosinophilic otitis media are unidentified. Therefore, we examined the kinds of the sinusitis combined with eosinophilic otitis media. We diagnosed 18 cases (male: 2 cases, female: 16 cases) (average age: 54.6 years old) as eosinophilic otitis media according to the diagnostic criteria. And, by the CT views of a paranasal sinus, blood tests, existence of the nasal polyp, etc, we investigated the kinds of sinusitis combined with eosinophilic otitis media. It turned out that bronchial asthma was combined with eosinophilic otitis media in 17 of 18 cases (airway hypersensitivity did sthenia of one case, but the asthma did not yet developed), and 6 cases were combined with aspirin induced asthma (AIA), and 3 cases were combined with Churg-Strauss syndromes (CSS). 10 case (55.6%) of 17 eosinophilic otitis media were combined with eosinophilic sinusitis. And 4 cases (22.2%) of 17 eosinophilic otitis media were combined with chronic sinusitis, 4 cases (22.2%) of 17 eosinophilic otitis media were not combined with sinusitis. We concluded that eosinophilic otitis media was not always combined with eosinophilic sinusitis. The idea of one airway one disease was not applied to this examination. (author)

Connexin 43 Expression on Peripheral Blood Eosinophils: Role of Gap Junctions in Transendothelial Migration

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Harissios Vliagoftis

2014-01-01

Full Text Available Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

Tomatidine Attenuates Airway Hyperresponsiveness and Inflammation by Suppressing Th2 Cytokines in a Mouse Model of Asthma

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Chieh-Ying Kuo

2017-01-01

Full Text Available Tomatidine is isolated from the fruits of tomato plants and found to have anti-inflammatory effects in macrophages. In the present study, we investigated whether tomatidine suppresses airway hyperresponsiveness (AHR and eosinophil infiltration in asthmatic mice. BALB/c mice were sensitized with ovalbumin and treated with tomatidine by intraperitoneal injection. Airway resistance was measured by intubation analysis as an indication of airway responsiveness, and histological studies were performed to evaluate eosinophil infiltration in lung tissue. Tomatidine reduced AHR and decreased eosinophil infiltration in the lungs of asthmatic mice. Tomatidine suppressed Th2 cytokine production in bronchoalveolar lavage fluid. Tomatidine also blocked the expression of inflammatory and Th2 cytokine genes in lung tissue. In vitro, tomatidine inhibited proinflammatory cytokines and CCL11 production in inflammatory BEAS-2B bronchial epithelial cells. These results indicate that tomatidine contributes to the amelioration of AHR and eosinophil infiltration by blocking the inflammatory response and Th2 cell activity in asthmatic mice.

The effect of omalizumab on eosinophilic inflammation of the respiratory tract in patients with allergic asthma.

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Kupryś-Lipińska, Izabela; Molińska, Katarzyna; Kuna, Piotr

2016-01-01

Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses of these drugs, even when administered systemically. Transbronchial biopsies and bronchoalveolar lavage performed in patients with steroid-resistant asthma have demonstrated higher levels of eosinophils and Th2-type cytokines (IL-4 and IL-5) compared to steroid-sensitive patients. Clinical studies have confirmed that the very effective treatment in these cases is therapy with omalizumab - an anti-IgE monoclonal antibody. The paper discusses the efficacy of omalizumab in reducing eosinophil number in peripheral blood and in the airways of asthmatic patients based on basic, clinical, observational studies and case reports. The significance of omalizumab therapy in asthma control and mechanisms that regulate the effects of omalizumab on eosinophils are evaluated.

Blood Eosinophil and Basophil Values Before and After Surgery for Eosinophilic-type Sinonasal Polyps.

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Brescia, Giuseppe; Parrino, Daniela; Zanotti, Claudia; Tealdo, Giulia; Barion, Umberto; Sfriso, Paolo; Marioni, Gino

2018-01-01

Background Blood eosinophil and basophil levels have recently been considered for the purpose of endotyping chronic rhinosinusitis with nasal polyps (CRSwNP). Histologically, eosinophilic-type CRSwNPs have been associated with high recurrence rates after treatment. Objective The present study was the first to compare blood eosinophil and basophil counts in eosinophilic-type CRSwNP patients before and after endoscopic sinus surgery. Methods The study concerned 79 consecutive patients with histologically confirmed eosinophilic-type CRSwNP treated with endoscopic sinus surgery. Results A significant drop in mean blood eosinophil counts and percentages occurred from before to after endoscopic sinus surgery in the cohort as a whole. Mean blood eosinophil counts and percentages were also reduced after surgery in the subcohorts of CRSwNP patients with (i) asthma, (ii) aspirin-exacerbated respiratory disease (AERD), and (iii) no allergy. Although blood eosinophil and basophil counts correlated directly before and after surgery, a statistical reduction in blood basophil counts and percentages after surgery emerged only in the subcohort of nonallergic CRSwNP patients. Conclusion Endoscopic sinus surgery can clear polyps, remove inflammatory tissue, and reduce inflammatory cytokine levels. Consistently with the biological mechanism described, endoscopic sinus surgery could coincide with a reduction in blood eosinophils in eosinophilic-type CRSwNP.

Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils?

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Martins, Patrícia Rocha; Nascimento, Rodolfo Duarte; Lopes, Júlia Guimarães; Santos, Mônica Morais; de Oliveira, Cleida Aparecida; de Oliveira, Enio Chaves; Martinelli, Patrícia Massara; d'Ávila Reis, Débora

2015-05-01

Megacolon is frequently observed in patients who develop the digestive form of Chagas disease. It is characterized by dilation of the rectum-sigmoid portion and thickening of the colon wall. Microscopically, the affected organ presents denervation, which has been considered as consequence of an inflammatory process that begins at the acute phase and persists in the chronic phase of infection. Inflammatory infiltrates are composed of lymphocytes, macrophages, natural killer cells, mast cells, and eosinophils. In this study, we hypothesized that mast cells producing tryptase could influence the migration and the activation of eosinophils at the site, thereby contributing to the immunopathology of the chronic phase. We seek evidence of interactions between mast cells and eosinophils through (1) evaluation of eosinophils, regarding the expression of PAR2, a tryptase receptor; (2) correlation analysis between densities of mast cells and eosinophils; and (3) ultrastructural studies. The electron microscopy studies revealed signs of activation of mast cells and eosinophils, as well as physical interaction between these cells. Immunohistochemistry and correlation analyses point to the participation of tryptase immunoreactive mast cells in the migration and/or survival of eosinophils at the affected organ.

Illicium verum Extract and Trans-Anethole Attenuate Ovalbumin-Induced Airway Inflammation via Enhancement of Foxp3+ Regulatory T Cells and Inhibition of Th2 Cytokines in Mice

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Yoon-Young Sung

2017-01-01

Full Text Available Illicium verum is used in traditional medicine to treat inflammation. The study investigates the effects of IVE and its component, trans-anethole (AET, on airway inflammation in ovalbumin- (OVA- induced asthmatic mice. Asthma was induced in BALB/c mice by systemic sensitization to OVA, followed by intratracheal, intraperitoneal, and aerosol allergen challenges. IVE and AET were orally administered for four weeks. We investigated the effects of treatment on airway hyperresponsiveness, IgE production, pulmonary eosinophilic infiltration, immune cell phenotypes, Th2 cytokine production in bronchoalveolar lavage, Th1/Th2 cytokine production in splenocytes, forkhead box protein 3 (Foxp3 expression, and lung histology. IVE and AET ameliorated OVA-driven airway hyperresponsiveness (p<0.01, pulmonary eosinophilic infiltration (p<0.05, mucus hypersecretion (p<0.01, and IL-4, IL-5, IL-13, and CCR3 production (p<0.05, as well as IgE levels (p<0.01. IVE and AET increased Foxp3 expression in lungs (p<0.05. IVE and AET reduced IL-4 and increased IFN-γ production in the supernatant of splenocyte cultures (p<0.05. Histological studies showed that IVE and AET inhibited eosinophilia and lymphocyte infiltration in lungs (p<0.01. These results indicate that IVE and AET exert antiasthmatic effects through upregulation of Foxp3+ regulatory T cells and inhibition of Th2 cytokines, suggesting that IVE may be a potential therapeutic agent for allergic lung inflammation.

Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils.

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Stubbs, Victoria E L; Schratl, Petra; Hartnell, Adele; Williams, Timothy J; Peskar, Bernhard A; Heinemann, Akos; Sabroe, Ian

2002-07-19

We investigated the actions of a panel of nonsteroidal anti-inflammatory drugs on eosinophils, basophils, neutrophils, and monocytes. Indomethacin alone was a potent and selective inducer of eosinophil and basophil shape change. In eosinophils, indomethacin induced chemotaxis, CD11b up-regulation, respiratory burst, and L-selectin shedding but did not cause up-regulation of CD63 expression. Pretreatment of eosinophils with indomethacin also enhanced subsequent eosinophil shape change induced by eotaxin, although treatment with higher concentrations of indomethacin resulted in a decrease in the expression of the major eosinophil chemokine receptor, CCR3. Indomethacin activities and cell selectivity closely resembled those of prostaglandin D(2) (PGD(2)). Eosinophil shape change in response to eotaxin was inhibited by pertussis toxin, but indomethacin- and PGD(2)-induced shape change responses were not. Treatment of eosinophils with specific inhibitors of phospholipase C (U-73122), phosphatidylinositol 3-kinase (LY-294002), and p38 mitogen-activated protein kinase (SB-202190) revealed roles for these pathways in indomethacin signaling. Indomethacin and its analogues may therefore provide a structural basis from which selective PGD(2) receptor small molecule antagonists may be designed and which may have utility in the treatment of allergic inflammatory disease.

Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils.

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Tamaki, Mami; Konno, Yasunori; Kobayashi, Yoshiki; Takeda, Masahide; Itoga, Masamichi; Moritoki, Yuki; Oyamada, Hajime; Kayaba, Hiroyuki; Chihara, Junichi; Ueki, Shigeharu

2014-07-01

Sexual dimorphism in asthma links the estrogen and allergic immune responses. The function of estrogen was classically believed to be mediated through its nuclear receptors, i.e., estrogen receptors (ERs). However, recent studies established the important roles of G-protein-coupled estrogen receptor (GPER/GPR30) as a novel membrane receptor for estrogen. To date, the role of GPER in allergic inflammation is poorly understood. The purpose of this study was to examine whether GPER might affect the functions of eosinophils, which play an important role in the pathogenesis of asthma. Here, we demonstrated that GPER was expressed in purified human peripheral blood eosinophils both at the mRNA and protein levels. Although GPER agonist G-1 did not induce eosinophil chemotaxis or chemokinesis, preincubation with G-1 enhanced eotaxin (CCL11)-directed eosinophil chemotaxis. G-1 inhibited eosinophil spontaneous apoptosis and caspase-3 activities. The anti-apoptotic effect was not affected by the cAMP-phospodiesterase inhibitor rolipram or phosphoinositide 3-kinase inhibitors. In contrast to resting eosinophils, G-1 induced apoptosis and increased caspase-3 activities when eosinophils were co-stimulated with IL-5. No effect of G-1 was observed on eosinophil degranulation in terms of release of eosinophil-derived neurotoxin (EDN). The current study indicates the functional capacities of GPER on human eosinophils and also provides the previously unrecognized mechanisms of interaction between estrogen and allergic inflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

Eosinophilic Endotype of Asthma.

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Aleman, Fernando; Lim, Hui Fang; Nair, Parameswaran

2016-08-01

Asthma is a heterogeneous disease that can be classified into different clinical endotypes, depending on the type of airway inflammation, clinical severity, and response to treatment. This article focuses on the eosinophilic endotype of asthma, which is defined by the central role that eosinophils play in the pathophysiology of the condition. It is characterized by elevated sputum and/or blood eosinophils on at least 2 occasions and by a significant response to treatments that suppress eosinophilia. Histopathologic demonstration of eosinophils in the airways provides the most direct diagnosis of eosinophilic asthma; but it is invasive, thus, impractical in clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Eosinophilic cystitis in children

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Liu Ming; Zhang Yuzhen; Li Yuhua; Wang Qiuyan; Xie Hua

2006-01-01

Objective: To discuss the clinical manifestations and CT findings of eosinophilic cystitis in children. Methods: Nine cases including Six boys and 3 girls, three to 13 years old, mean age of 8.3- year, have symptoms of hematuria, irritative voiding, dysuria and abdominal pain. The eosinophilic cystitis was pathologically proved in 7 patients and eosinophilic granulomatous cystitis in 2 patients, which based on cystoscopic tissue biopsy or surgery retrospectively. Results: Local thickened bladder walls or nodular and sessile masses along the bladder dome showed in four cases with eosinophilic granulomatous cystitis, and the diffusely irregularly thickened bladder wails showed on CT scans in the rest 5 cases with eosinophilic cystitis. Conclusion: CT findings are helpful to reveal the site, size and other features of eosinophilic cystitis in children. But biopsy of the lesion is necessary to rule out other bladder tumor and selecting the proper management. (authors)

Eosinophilic myocarditis due to Churg-Strauss syndrome mimicking reversible dilated cardiomyopathy.

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Chen, Ming-xian; Yu, Bi-lian; Peng, Dao-quan; Zhou, Sheng-hua

2014-01-01

A 41-year-old woman with a history of asthma arrived at the emergency room of our hospital with dyspnea. The electrocardiogram showed no specific results. Echocardiography defects revealed an obvious decrease in the left ventricular systolic function and enlargement of the left chamber. We initially considered her condition to be dilated cardiomyopathy. However, she had eosinophilia in the peripheral blood and elevated cardiac enzymes. The coronary angiography showed normal coronary arteries. Single photon emission computed tomography (SPECT) showed infiltrative myocardial disease. She was then diagnosed with eosinophil infiltrations. Combined with peripheral nerve injury and lung involvement, she was diagnosed as having Churg-Strauss syndrome. After initiating prednisone treatment, her eosinophilia and rising cardiac enzymes recovered to normal, and both her echocardiographic abnormalities and symptoms noticeably improved. Copyright © 2014 Elsevier Inc. All rights reserved.

Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor.

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Willart, M A M; van Nimwegen, M; Grefhorst, A; Hammad, H; Moons, L; Hoogsteden, H C; Lambrecht, B N; Kleinjan, A

2012-12-01

Ursodeoxycholic acid (UDCA) is the only known beneficial bile acid with immunomodulatory properties. Ursodeoxycholic acid prevents eosinophilic degranulation and reduces eosinophil counts in primary biliary cirrhosis. It is unknown whether UDCA would also modulate eosinophilic inflammation outside the gastrointestinal (GI) tract, such as eosinophilic airway inflammation seen in asthma. The working mechanism for its immunomodulatory effect is unknown. The immunosuppressive features of UDCA were studied in vivo, in mice, in an ovalbumin (OVA)-driven eosinophilic airway inflammation model. To study the mechanism of action of UDCA, we analyzed the effect of UDCA on eosinophils, T cells, and dendritic cell (DCs). DC function was studied in greater detail, focussing on migration and T-cell stimulatory strength in vivo and interaction with T cells in vitro as measured by time-lapse image analysis. Finally, we studied the capacity of UDCA to influence DC/T cell interaction. Ursodeoxycholic acid treatment of OVA-sensitized mice prior to OVA aerosol challenge significantly reduced eosinophilic airway inflammation compared with control animals. DCs expressed the farnesoid X receptor for UDCA. Ursodeoxycholic acid strongly promoted interleukin (IL)-12 production and enhanced the migration in DCs. The time of interaction between DCs and T cells was sharply reduced in vitro by UDCA treatment of the DCs resulting in a remarkable T-cell cytokine production. Ursodeoxycholic acid-treated DCs have less capacity than saline-treated DCs to induce eosinophilic inflammation in vivo in Balb/c mice. Ursodeoxycholic acid has the potency to suppress eosinophilic inflammation outside the GI tract. This potential comprises to alter critical function of DCs, in essence, the effect of UDCA on DCs through the modulation of the DC/T cell interaction. © 2012 John Wiley & Sons A/S.

Mesocarbon microbead based graphite for spherical fuel element to inhibit the infiltration of liquid fluoride salt in molten salt reactor

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Zhong, Yajuan, E-mail: yajuan.zhong@gmail.com [Center for Thorium Molten Salt Reactor System, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); CAS Key Laboratory of Carbon Materials, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001 (China); Zhang, Junpeng [CAS Key Laboratory of Carbon Materials, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001 (China); Lin, Jun, E-mail: linjun@sinap.ac.cn [Center for Thorium Molten Salt Reactor System, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Xu, Liujun [Center for Thorium Molten Salt Reactor System, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Zhang, Feng; Xu, Hongxia; Chen, Yu; Jiang, Haitao; Li, Ziwei; Zhu, Zhiyong [Center for Thorium Molten Salt Reactor System, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Guo, Quangui [CAS Key Laboratory of Carbon Materials, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001 (China)

2017-07-15

Mesocarbon microbeads (MCMB) and quasi-isostatic pressing method were used to prepare MCMB based graphite (MG) for spherical fuel element to inhibit the infiltration of liquid fluoride salt in molten salt reactor (MSR). Characteristics of mercury infiltration and molten salt infiltration in MG were investigated and compared with A3-3 (graphite for spherical fuel element in high temperature gas cooled reactor) to identify the infiltration behaviors. The results indicated that MG had a low porosity about 14%, and an average pore diameter of 96 nm. Fluoride salt occupation of A3-3 (average pore diameter was 760 nm) was 10 wt% under 6.5 atm, whereas salt gain did not infiltrate in MG even up to 6.5 atm. It demonstrated that MG could inhibit the infiltration of liquid fluoride salt effectively. Coefficient of thermal expansion (CTE) of MG lies in 6.01 × 10{sup −6} K{sup −1} (α{sub ∥}) and 6.15 × 10{sup −6} K{sup −1} (α{sub ⊥}) at the temperature range of 25–700 °C. The anisotropy factor of MG calculated by CTE maintained below 1.02, which could meet the requirement of the spherical fuel element (below 1.30). The constant isotropic property of MG is beneficial for the integrity and safety of the graphite used in the spherical fuel element for a MSR.

Mesocarbon microbead based graphite for spherical fuel element to inhibit the infiltration of liquid fluoride salt in molten salt reactor

International Nuclear Information System (INIS)

Zhong, Yajuan; Zhang, Junpeng; Lin, Jun; Xu, Liujun; Zhang, Feng; Xu, Hongxia; Chen, Yu; Jiang, Haitao; Li, Ziwei; Zhu, Zhiyong; Guo, Quangui

2017-01-01

Mesocarbon microbeads (MCMB) and quasi-isostatic pressing method were used to prepare MCMB based graphite (MG) for spherical fuel element to inhibit the infiltration of liquid fluoride salt in molten salt reactor (MSR). Characteristics of mercury infiltration and molten salt infiltration in MG were investigated and compared with A3-3 (graphite for spherical fuel element in high temperature gas cooled reactor) to identify the infiltration behaviors. The results indicated that MG had a low porosity about 14%, and an average pore diameter of 96 nm. Fluoride salt occupation of A3-3 (average pore diameter was 760 nm) was 10 wt% under 6.5 atm, whereas salt gain did not infiltrate in MG even up to 6.5 atm. It demonstrated that MG could inhibit the infiltration of liquid fluoride salt effectively. Coefficient of thermal expansion (CTE) of MG lies in 6.01 × 10 −6 K −1 (α ∥ ) and 6.15 × 10 −6 K −1 (α ⊥ ) at the temperature range of 25–700 °C. The anisotropy factor of MG calculated by CTE maintained below 1.02, which could meet the requirement of the spherical fuel element (below 1.30). The constant isotropic property of MG is beneficial for the integrity and safety of the graphite used in the spherical fuel element for a MSR.

Eosinophils Regulate Interferon Alpha Production in Plasmacytoid Dendritic Cells Stimulated with Components of Neutrophil Extracellular Traps.

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Skrzeczynska-Moncznik, Joanna; Zabieglo, Katarzyna; Bossowski, Jozef P; Osiecka, Oktawia; Wlodarczyk, Agnieszka; Kapinska-Mrowiecka, Monika; Kwitniewski, Mateusz; Majewski, Pawel; Dubin, Adam; Cichy, Joanna

2017-03-01

Eosinophils constitute an important component of helminth immunity and are not only associated with various allergies but are also linked to autoinflammatory disorders, including the skin disease psoriasis. Here we demonstrate the functional relationship between eosinophils and plasmacytoid dendritic cells (pDCs) as related to skin diseases. We previously showed that pDCs colocalize with neutrophil extracellular traps (NETs) in psoriatic skin. Here we demonstrate that eosinophils are found in psoriatic skin near neutrophils and NETs, suggesting that pDC responses can be regulated by eosinophils. Eosinophils inhibited pDC function in vitro through a mechanism that did not involve cell contact but depended on soluble factors. In pDCs stimulated by specific NET components, eosinophil-conditioned media attenuated the production of interferon α (IFNα) but did not affect the maturation of pDCs as evidenced by the unaltered expression of the costimulatory molecules CD80 and CD86. As pDCs and IFNα play a key role in autoimmune skin inflammation, these data suggest that eosinophils may influence autoinflammatory responses through their impact on the production of IFNα by pDCs.

Non-Eosinophilic Nasal Polyps Shows Increased Epithelial Proliferation and Localized Disease Pattern in the Early Stage.

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Dong-Kyu Kim

Full Text Available Non-eosinophilic nasal polyps (NPs show less inflammatory changes and are less commonly associated with lower airway inflammatory disorders such as asthma, compared with eosinophilic NPs. However, the development of non-eosinophilic NPs which is a predominant subtype in Asian population still remains unclear.A total of 81 patients (45 with non-eosinophilic NPs and 36 with eosinophilic NPs were enrolled. Clinical information and computed tomography (CT, endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE levels and for mRNA expression levels of interleukin (IL-4, IL-5, IL-13, interferon (IFN-γ, tumor necrosis factor (TNF-α, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF-β1, TGF-β2, TGF-β3, and periostin. Immunostaining assessment of Ki-67 as a proliferation marker was performed.We found that epithelial in-growing patterns such as pseudocysts were more frequently observed in histological and endoscopic evaluations of non-eosinophilic NPs, which was linked to increase epithelial staining of Ki-67, a proliferating marker. Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs. To investigate the developmental course of each subtype, CT was analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more localized pattern and maxillary sinus involvement, but lesser olfactory involvement in early stage whereas eosinophilic NPs were characterized by diffuse ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M CT scores, indicating ethmoidal dominant involvement, were one of surrogate markers for eosinophilic NP. E/M CT scores was positively correlated with levels of TH2 inflammatory markers, including IL-4, IL-5, periostin mRNA expression and total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- γ were inversely correlated. Moreover, if the combinatorial algorithm meet the three

Evaluation of mast cells, eosinophils, blood capillaries in oral lichen planus and oral lichenoid mucositis.

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Reddy, D Santhosh; Sivapathasundharam, B; Saraswathi, T R; SriRam, G

2012-01-01

Mast cells are granule containing secretory cells present in oral mucosal and connective tissue environment. Oral lichen planus and oral lichenoid lesions are commonly occurring oral diseases and have some similarity clinically and histologically. Both are characterized by an extensive sub epithelial infiltrate of T cells, together with mast cells, eosinophils and blood capillaries. In this study mast cell and eosinophil densities along with number of blood capillaries were studied to find out if they could aid in histopathological distinction between oral lichen planus and lichenoid mucositis. To enumerate mast cells and compare the status of Mast Cells (Intact or Degranulated) in Lichen planus, Lichenoid mucositis and normal buccal mucosa in tissue sections stained with Toluidine Blue, and also to enumerate Eosinophils and blood capillaries in tissue sections stained with H and E. The study group included 30 cases each of oral lichen planus and oral lichenoid mucositis. 10 cases of clinically normal oral buccal mucosa formed the control group. All the sections were stained with Toluidine blue and H and E separately. Histopathological analysis was done using binocular light microscope equipped with square ocular grid to standardize the field of evaluation. The result of the study showed. · Significant increase in number of mast cells in oral lichen planus and oral lichenoid mucositis compared to normal buccal mucosa. · Significant increase of intact mast cells suepithelially within the inflammatory cell infiltrate in oral lichen planus compared to oral lichenoid mucositis. · Significant increase of degranulated mast cells in oral lichenoid mucositis to oral lichen planus, and increase in number of eosinophil densities in oral lichenoid mucositis compared to oral lichen planus. · Significant increase in number of capillaries in oral lichenoid mucositis compared to oral lichen planus. The findings of increased number of intact mast cells sub epithelially in oral

Differentiating Focal Eosinophilic Infiltration from Metastasis in the Liver with Gadoxetic Acid-Enhanced Magnetic Resonance Imaging

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Lee, Mi Hee; Kim, Seong Hyun; Kim, Hee Jung; Lee, Min Woo; Lee, Won Jae [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2011-08-15

To determine the most useful findings of gadoxetic acid-enhanced 3.0 Tesla (T) MRI for differentiating focal eosinophilic infiltration (FEI) from hepatic metastasis with verification of their usefulness. Pathologically or clinically proven 39 FEIs from 25 patients and 79 hepatic metastases from 51 patients were included in the study. Gadoxetic acid-enhanced 3.0T MRI was performed in all cancer patients. Size differences measured between T2-weighted and hepatobiliary-phase images for lesions > 1 cm and morphologic findings (margin, shape, signal intensity on T1- and T2-weighted images, enhancement pattern on dynamic images, and target appearance on hepatobiliary-phase images) were compared between two groups via Student's t test as well as univariate and multivariate analyses. Diagnostic predictive values of two observers for differentiating two groups were assessed before (session 1) and after (session 2) recognition of results. Mean size difference (2.1 mm) in FEIs between the two images was significantly greater than for metastases (0.7 mm) (p < 0.05). An ill-defined margin and isointensity on T1-weighted images were independently significant morphologic findings (p < 0.05) for differentiating the two groups. All observers achieved a higher diagnostic accuracy in session 2 (97% and 98%) than session 1 (92% and 89%) with statistical significance in observer 2 (p < 0.05). All observers had significantly higher sensitivities (95%) and negative predictive values (NPVs) (98%) in session 2 than in session 1 (sensitivity, 74% in two observers; NPV, 89% and 88%) (p < 0.05). With the size change, an ill-defined margin and isointensity on T1-weighted images are the most useful findings for differentiating FEI from hepatic metastasis on gadoxetic acid-enhanced 3.0T MRI.

Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

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Liu, L Y; Wang, H; Xenakis, J J; Spencer, L A

2015-07-01

Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eosinophilic Lung Disorders

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... problems characterized by having an increased number of eosinophils (white blood cells) in the lungs. These white ... category of pneumonias that feature increased numbers of eosinophils in the lung tissue. Pneumonia is an inflammatory ...

Human Eosinophils Express Functional CCR7

Science.gov (United States)

Ueki, Shigeharu; Estanislau, Jessica; Weller, Peter F.

2013-01-01

Human eosinophils display directed chemotactic activity toward an array of soluble chemokines. Eosinophils have been observed to migrate to draining lymph nodes in experimental models of allergic inflammation, yet it is unknown whether eosinophils express CCR7, a key chemokine receptor in coordinating leukocyte trafficking to lymph nodes. The purpose of this study is to demonstrate expression of CCR7 by human eosinophils and functional responses to CCL19 and CCL21, the known ligands of CCR7. Human eosinophils were purified by negative selection from healthy donors. CCR7 expression of freshly purified, unstimulated eosinophils and of IL-5–primed eosinophils was determined by flow cytometry and Western blot. Chemotaxis to CCL19 and CCL21 was measured in transwell assays. Shape changes to CCL19 and CCL21 were analyzed by flow cytometry and microscopy. Calcium fluxes of fluo-4 AM–loaded eosinophils were recorded by flow cytometry after chemokine stimulation. ERK phosphorylation of CCL19- and CCL21-stimulated eosinophils was measured by Western blot and Luminex assay. Human eosinophils expressed CCR7 as demonstrated by flow cytometry and Western blots. Eosinophils exhibited detectable cell surface expression of CCR7. IL-5–primed eosinophils exhibited chemotaxis toward CCL19 and CCL21 in a dose-dependent fashion. Upon stimulation with CCL19 or CCL21, IL-5–primed eosinophils demonstrated dose-dependent shape changes with polarization of F-actin and exhibited calcium influxes. Finally, primed eosinophils stimulated with CCL19 or CCL21 exhibited increased phosphorylation of ERK in response to both CCR7 ligands. We demonstrate that human eosinophils express CCR7 and have multipotent responses to the known ligands of CCR7. PMID:23449735

External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma.

Science.gov (United States)

Wagener, A H; de Nijs, S B; Lutter, R; Sousa, A R; Weersink, E J M; Bel, E H; Sterk, P J

2015-02-01

Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE(NO) show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic inflammation. Quantifying the mutual relationships of blood eosinophils, FE(NO), and serum periostin with sputum eosinophils by external validation in two independent cohorts across various severities of asthma. The first cohort consisted of 110 patients with mild to moderate asthma (external validation cohort). The replication cohort consisted of 37 patients with moderate to severe asthma. Both cohorts were evaluated cross-sectionally. Sputum was induced for the assessment of eosinophils. In parallel, blood eosinophil counts, serum periostin concentrations and FENO were assessed. The diagnostic accuracy of these markers to identify eosinophilic asthma (sputum eosinophils ≥3%) was calculated using receiver operating characteristics area under the curve (ROC AUC). In the external validation cohort, ROC AUC for blood eosinophils was 89% (peosinophilic from non-eosinophilic airway inflammation (ROC AUC=55%, p=0.44). When combining these three variables, no improvement was seen. The diagnostic value of blood eosinophils was confirmed in the replication cohort (ROC AUC 85%, peosinophils had the highest accuracy in the identification of sputum eosinophilia in asthma. The use of blood eosinophils can facilitate individualised treatment and management of asthma. NTR1846 and NTR2364. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chronic eosinophilic pneumonia: CT findings

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Gutierrez, Haydee; Beccar Varela, Lucia; De Felippi, Maria S.

2002-01-01

Objective: To assess the usefulness of computerized tomography (CT) in the diagnosis of chronic eosinophilic pneumonia. Material and Methods: A double helical CT was performed in 6 patients referred to our center because of a chest X-ray with pulmonary infiltrates. Clinical presentation was cough, fever and eosinophilia in peripheral blood. Patients' age ranged from 25 to 55 years; 4 were women and 2 were men, one of the latter had a history of bronchial asthma. All patients received treatment with corticosteroids, with remission of the clinical and radiological parameters. Three patients underwent a control CT. Results: Findings consisted in focal parenchymal alterations, with areas of pulmonary consolidation and areas of 'ground glass' appearance; both patterns coexisted in certain areas. In 3 cases the lesions extended from the apices to the pulmonary bases, with predominance of the upper and middle fields. In 1 patient, there was frank predominance in the left hemi thorax. In another patient, who had a history of asthma, there were signs of pulmonary hyperinflation, with diffuse thickening of the bronchial walls, added to the previously mentioned findings, which involved the entire lung. In the mediastinum, 1 patient had lymph nodes larger than 1 cm, 3 had lymph nodes that were not enlarged but were more numerous than usual, and in the remaining patients no lymph nodes were found. The control CT's showed almost total resolution of the pulmonary infiltrates. Conclusion: The combination of eosinophilia and characteristic pulmonary infiltrates with a likely clinical presentation, associated with an optimal response to treatment with corticosteroids allows to make a reliable diagnosis and avoids the need for a pulmonary biopsy. (author)

Eosinophils in lichen sclerosus et atrophicus.

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Keith, Phillip J; Wolz, Michael M; Peters, Margot S

2015-10-01

The classic histopathologic features of lichen sclerosus et atrophicus (LS) include lymphoplasmacytic inflammation below a zone of dermal edema and sclerosis. The presence of eosinophils in LS has received little attention, but the finding of tissue eosinophils, particularly eosinophilic spongiosis in LS, has been suggested as a marker for the coexistence of autoimmune bullous disease or allergic contact dermatitis (or both). We sought to determine whether the histopathologic presence of dermal eosinophils or eosinophilic spongiosis (or both) in biopsies from patients with LS is associated with autoimmune bullous disease, autoimmune connective tissue disease or allergic contact dermatitis. A retrospective review of the histopathology and medical records of 235 patients with LS who were evaluated from June 1992 to June 2012 was performed. Sixty-nine patients (29%) had eosinophils on histopathology. Among patients with associated diseases, a statistically significant association between the eosinophil cohort and the cohort without eosinophils was not detected. The importance of eosinophils is uncertain, but our data suggest that the finding of tissue eosinophils alone is not sufficient to prompt an extensive workup for additional diagnoses. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Curcumin ameliorates macrophage infiltration by inhibiting NF-κB activation and proinflammatory cytokines in streptozotocin induced-diabetic nephropathy

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Suzuki Kenji

2011-06-01

Full Text Available Abstract Background Chronic inflammation plays an important role in the progression of diabetic nephropathy (DN and that the infiltration of macrophages in glomerulus has been implicated in the development of glomerular injury. We hypothesized that the plant polyphenolic compound curcumin, which is known to exert potent anti-inflammatory effect, would ameliorate macrophage infiltration in streptozotocin (STZ-induced diabetic rats. Methods Diabetes was induced with STZ (55 mg/kg by intraperitoneal injection in rats. Three weeks after STZ injection, rats were divided into three groups, namely, control, diabetic, and diabetic treated with curcumin at 100 mg/kg/day, p.o., for 8 weeks. The rats were sacrificed 11 weeks after induction of diabetes. The excised kidney was used to assess macrophage infiltration and expression of various inflammatory markers. Results At 11 weeks after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood glucose, blood urea nitrogen and proteinuria, along with marked reduction in the body weight. All of these abnormalities were significantly reversed by curcumin. Hyperglycemia induced the degradation of IκBα and NF-κB activation and as a result increased infiltration of macrophages (52% as well as increased proinflammatory cytokines: TNF-α and IL-1β. Curcumin treatment significantly reduced macrophage infiltration in the kidneys of diabetic rats, suppressed the expression of above proinflammatory cytokines and degradation of IκBα. In addition, curcumin treatment also markedly decreased ICAM-1, MCP-1 and TGF-β1 protein expression. Moreover, at nuclear level curcumin inhibited the NF-κB activity. Conclusion Our results suggested that curcumin treatment protect against the development of DN in rats by reducing macrophage infiltration through the inhibition of NF-κB activation in STZ-induced diabetic rats.

Eosinophilic Esophagitis in a Developing Country: Is It Different from Developed Countries?

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Abdulrahman Al-Hussaini

2013-01-01

Full Text Available Background and Objective. Despite the extensive reporting of eosinophilic esophagitis (EoE from industrialized developed countries, reports from developing countries are rare. The aim of our study was to determine the epidemiological, clinical, and endoscopic features of EoE and response to therapy in children and adults from a developing country, Saudi Arabia. Methods. We identified patients diagnosed with EoE in our center from 2004 to 2011. EoE was defined as esophageal mucosal infiltration with a peak eosinophil count ≥15 eosinophils/high-powered field. Results. Forty-five patients were diagnosed with EoE (37 children and 8 adults; 36 males; median age 10.5 years, range from 1–37 years. Feeding difficulty, vomiting/regurgitation, and failure to thrive predominated in young children, whereas dysphagia and food impactions predominated in older children and adults. Allergy testing revealed food sensitization in 12 of 15 patients (80%; 3 responded to elemental formula, while 8 failed to respond to dietary manipulation after the allergy testing. Thirty-nine patients achieved remission by swallowed inhaled fluticasone. The majority of patients experienced a recurrence of symptoms upon the discontinuation of fluticasone. Conclusion. Our data indicate that EoE is increasingly recognized in Saudi Arabia and show many similarities to data from North America and Europe.

Beta 2-adrenergic receptors on eosinophils. Binding and functional studies

International Nuclear Information System (INIS)

Yukawa, T.; Ukena, D.; Kroegel, C.; Chanez, P.; Dent, G.; Chung, K.F.; Barnes, P.J.

1990-01-01

We have studied the binding characteristics and functional effects of beta-adrenoceptors on human and guinea pig eosinophils. We determined the binding of the beta-antagonist radioligand [125I]pindolol (IPIN) to intact eosinophils obtained from the peritoneal cavity of guinea pigs and from blood of patients with eosinophilia. Specific binding was saturable, and Scatchard analysis showed a single binding site with a dissociation constant (Kd) of 24.6 pM and maximal number of binding sites (Bmax) of 7,166 per cell. ICI 118,551, a beta 2-selective antagonist, inhibited IPIN binding with a Ki value of 0.28 nM and was approximately 5,000-fold more effective than the beta 1-selective antagonist, atenolol. Isoproterenol increased cAMP levels about 5.5-fold above basal levels (EC50 = 25 microM); albuterol, a beta 2-agonist, behaved as a partial agonist with a maximal stimulation of 80%. Binding to human eosinophils gave similar results with a Kd of 25.3 pM and a Bmax corresponding to 4,333 sites per cell. Incubation of both human and guinea pig eosinophils with opsonized zymosan (2 mg/ml) or with phorbol myristate acetate (PMA) (10(-8) and 10(-6) M) resulted in superoxide anion generation and the release of eosinophil peroxidase; albuterol (10(-7) to 10(-5) M) had no inhibitory effect on the release of these products. Thus, eosinophils from patients with eosinophilia and from the peritoneal cavity of guinea pigs possess beta-receptors of the beta 2-subtype that are coupled to adenylate cyclase; however, these receptors do not modulate oxidative metabolism or degranulation. The possible therapeutic consequences of these observations to asthma are discussed

Eosinophil cationic protein stimulates and major basic protein inhibits airway mucus secretion

DEFF Research Database (Denmark)

Lundgren, J D; Davey, R T; Lundgren, B

1991-01-01

Possible roles of eosinophil (EO) products in modulating the release of mucus from airway explants were investigated. Cell- and membrane-free lysates from purified human EOs (1 to 20 x 10(5)) caused a dose-dependent release of respiratory glycoconjugates (RGC) from cultured feline tracheal explants...

Associations between inflammatory cells infiltrating the ethmoid sinus mucosa, and nasal polyp size and grade of ethmoid sinus opacification on CT images in chronic sinusitis

International Nuclear Information System (INIS)

Imajima, Naotoshi; Watanabe, So; Furuta, Atsuko; Shimizu, Toshiyuki; Yamada, Naohiro; Mochizuki, Yuichiro; Suzaki, Harumi

2009-01-01

We investigated the types and numbers of inflammatory cells that infiltrated the ethmoid sinus mucosa in cases of chronic sinusitis in order to identify any associations with nasal polyp size and the grade of ethmoid sinus opacification on computer tomography images. The subjects were patients with chronic sinusitis who underwent endoscopic sinus surgery. Seventeen subjects also had bronchial asthma as a complication (six with aspirin-induced asthma, 11 with another form of asthma) and 24 did not have bronchial asthma as a complication (16 with allergic rhinitis, 8 with chronic sinusitis alone). The nasal polyps in the patients with bronchial asthma were significantly larger than those in the patients without bronchial asthma. Investigation of the numbers of infiltrating inflammatory cells according to polyp size revealed significantly more eosinophils as polyp size increased. In addition, infiltration of significantly more mast cells was observed when the polyps were large. Assessment of the grade of opacification of the ethmoid sinuses on computer tomography images showed a significantly higher grade of opacification in the patients with bronchial asthma than in the patients without bronchial asthma. Comparisons between the grade of opacification of the ethmoid sinuses and the number of infiltrating inflammatory cells revealed significantly more infiltrating eosinophils and mast cells in the patients with intense ethmoid sinus opacification. The above findings suggest that eosinophils and mast cells play a major role in forming the persistent inflammation of the sinus mucosa and nasal polyp tissue of patients with chronic sinusitis complicated by bronchial asthma. (author)

Eosinophilic panniculitis.

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Samlaska, C P; de Lorimier, A J; Heldman, L S

1995-03-01

Eosinophillic panniculitis is a poorly defined entity with variable clinical features. We report a case of rapidly enlarging, asymptomatic subcutaneous scalp nodules in a 6-year-old black boy with atopic dermatitis. The nodules resolved spontaneously over two to three days. Biopsy specimens were remarkable for eosinophilic panniculitis without evidence of epidermal change or vasculitis. We believe that this is the youngest reported patient with this disorder.

External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma

NARCIS (Netherlands)

Wagener, A. H.; de Nijs, S. B.; Lutter, R.; Sousa, A. R.; Weersink, E. J. M.; Bel, E. H.; Sterk, P. J.

2015-01-01

Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE(NO) show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic

Esophageal Rupture as a Primary Manifestation in Eosinophilic Esophagitis

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Natalia Vernon

2014-01-01

Full Text Available Eosinophilic esophagitis (EoE is a chronic inflammatory process characterized by symptoms of esophageal dysfunction and, histologically, by eosinophilic infiltration of the esophagus. In adults, it commonly presents with dysphagia, food impaction, and chest or abdominal pain. Chronic inflammation can lead to diffuse narrowing of the esophageal lumen which may cause food impaction. Endoscopic procedures to relieve food impaction may lead to complications such as esophageal perforation due to the friability of the esophageal mucosa. Spontaneous transmural esophageal rupture, also known as Boerhaave’s syndrome, as a primary manifestation of EoE is rare. In this paper, we present two adult patients who presented with esophageal perforation as the initial manifestation of EoE. This rare complication of EoE has been documented in 13 other reports (11 adults, 2 children and only 1 of the patients had been previously diagnosed with EoE. A history of dysphagia was present in 1 of our patients and in the majority of previously documented patients. Esophageal perforation is a potentially severe complication of EoE. Patients with a history of dysphagia and patients with spontaneous esophageal perforation should warrant an evaluation for EoE.

Functions of tissue-resident eosinophils.

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Weller, Peter F; Spencer, Lisa A

2017-12-01

Eosinophils are a prominent cell type in particular host responses such as the response to helminth infection and allergic disease. Their effector functions have been attributed to their capacity to release cationic proteins stored in cytoplasmic granules by degranulation. However, eosinophils are now being recognized for more varied functions in previously underappreciated diverse tissue sites, based on the ability of eosinophils to release cytokines (often preformed) that mediate a broad range of activities into the local environment. In this Review, we consider evolving insights into the tissue distribution of eosinophils and their functional immunobiology, which enable eosinophils to secrete in a selective manner cytokines and other mediators that have diverse, 'non-effector' functions in health and disease.

Phospholipase D-derived phosphatidic acid is involved in the activation of the CD11b/CD18 integrin in human eosinophils

NARCIS (Netherlands)

Tool, A. T.; Blom, M.; Roos, D.; Verhoeven, A. J.

1999-01-01

Priming of human eosinophils is an essential event for the respiratory burst induced by serum-opsonized particles [serum-treated zymosan (STZ)]. In this study we have found that treatment of eosinophils with platelet-activating factor (PAF) leads to activation of phospholipase D. Inhibition of the

The Regulatory Function of Eosinophils.

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Wen, Ting; Rothenberg, Marc E

2016-10-01

Eosinophils are a minority circulating granulocyte classically viewed as being involved in host defense against parasites and promoting allergic reactions. However, a series of new regulatory functions for these cells have been identified in the past decade. During homeostasis, eosinophils develop in the bone marrow and migrate from the blood into target tissues following an eotaxin gradient, with interleukin-5 being a key cytokine for eosinophil proliferation, survival, and priming. In multiple target tissues, eosinophils actively regulate a variety of immune functions through their vast arsenal of granule products and cytokines, as well as direct cellular interaction with cells in proximity. The immunologic regulation of eosinophils extends from innate immunity to adaptive immunity and also involves non-immune cells. Herein, we summarize recent findings regarding novel roles of murine and human eosinophils, focusing on interactions with other hematopoietic cells. We also review new experimental tools available and remaining questions to uncover a greater understanding of this enigmatic cell.

Radioimmunoassay of human eosinophil cationic protein

International Nuclear Information System (INIS)

Venge, P.; Roxin, L.E.; Olsson, I.

1977-01-01

A radioimmunosorbent assay has been developed which allows the detection in serum of a cationic protein derived from eosinophil granulocytes. In 34 healthy individuals the mean level was 31 μg/l. with a range of 5 to 55 μg/l. The serum concentration of 'eosinophil' cationic protein was correlated (P<0.001) to the number of eosinophil granulocytes in peripheral blood. Quantitiation of 'eosinophil' cationic protein in serum might be useful in the study of eosinophil granulocyte turnover and function in vivo. (author)

Eosinophilic Esophagitis (EoE)

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... specific responses in allergy? » Dietary Therapy and Nutrition Management of Eosinophilic Esophagitis: A Work Group Report of the American Academy of Allergy, Asthma, and Immunology » Eosinophilic esophagitis can ...

Th2 cytokines and asthma — The role of interleukin-5 in allergic eosinophilic disease

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Chapman Richard W

2001-03-01

Full Text Available Abstract Interleukin-5 is produced by a number of cell types, and is responsible for the maturation and release of eosinophils in the bone marrow. In humans, interleukin-5 is a very selective cytokine as a result of the restricted expression of the interleukin-5 receptor on eosinophils and basophils. Eosinophils are a prominent feature in the pulmonary inflammation that is associated with allergic airway diseases, suggesting that inhibition of interleukin-5 is a viable treatment. The present review addresses the data that relate interleukin-5 to pulmonary inflammation and function in animal models, and the use of neutralizing anti-interleukin-5 monoclonal antibodies for the treatment of asthma in humans.

Unusual presentations of eosinophilic gastroenteritis: Case series and review of literature

Institute of Scientific and Technical Information of China (English)

Rafiq A Sheikh; Thomas P Prindiville; R Erick Pecha; Boris H Ruebner

2009-01-01

Eosinophilic gastroenteritis (EG) is an uncommon disease characterized by focal or diffuse eosinophilic infiltration of the gastrointestinal tract, and is usually associated with dyspepsia, diarrhea and peripheral eosinophilia. Diffuse gastrointestinal tract and colonic involvement are uncommon. The endoscopic appearance may vary from normal to mucosal nodularity and ulceration. Gastrointestinal obstruction is unusual and is associated with predominantly muscular disease. We present five unusual cases of EG associated with gastric outlet and duodenal obstruction. Two cases presented with acute pancreatitis and one had a history of pancreatitis. Four cases responded well to medical therapy and one had recurrent gastric outlet obstruction that required surgery. Four out of the five cases had endoscopic and histological evidence of esophagitis and two had colitis. Two patients had ascites. These cases reaffirm that EG is a disorder with protean manifestations and may involve the entire gastrointestinal tract. Gastric outlet and/or small bowel obstruction is an important though uncommon presentation of EG. It may also present as esophagitis, gastritis with polypoid lesions, ulcers or erosions, colitis and pancreatitis and may mimic malignancy.

The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells.

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Lee, Ji-Sook; Yang, Eun Ju; Kim, In Sik

2009-12-01

Idiopathic hypereosinophilc syndrome is a disorder associated with clonally eosinophilic proliferation. The importance of FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) in the pathogenesis and classification of HES has been recently reported. In this study, we investigated the contribution of monocyte chemoattractant protein-1 (MCP-1)/CCL2 to chemotactic activity and protein kinase C delta (PKC delta in the human eosinophilic leukemia cell line EoL-1. These cells express CCR2 protein among the CC chemokine receptors (CCR1-5). MCP-1 induces strong migration of EoL-1 cells and the chemotaxis signal in response to MCP-1 involves a G(i)/G(o) protein, phospholipase C (PLC), PKC delta, p38 MAPK and NF-kappaB. MCP-1 activates p38 MAPK via G(i)/G(o) protein, PLC and PKC delta cascade. MCP-1 also induces NF-kappaB translocation and the activation is inhibited by PKC delta activation. The increase in the basal expression and activity of PKC delta in EoL-1 cells, compared to normal eosinophils, inhibits apoptosis in EoL-1 cells. Anti-apoptotic mechanism of PKC delta is related to inhibition of caspase 3 and caspase 9, but not to FIP1L1-PDGFRA. PKC delta functions as an anti-apoptotic molecule, and is involved in EoL-1 cell movement stimulated by MCP-1. This study contributes to an understanding of MCP-1 in eosinophil biology and pathogenic mechanism of eosinophilic disorders.

Inhibiting focal adhesion kinase (FAK) blocks IL-4 induced VCAM-1 expression and eosinophil recruitment in vitro and in vivo.

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Aulakh, Gurpreet K; Petri, Björn; Wojcik, Katarzyna M; Colarusso, Pina; Lee, James J; Patel, Kamala D

2018-04-06

Leukocyte recruitment plays a critical role during both normal inflammation and chronic inflammatory diseases, and ongoing studies endeavor to better understand the complexities of this process. Focal adhesion kinase (FAK) is well known for its role in cancer, yet it also has been shown to regulate aspects of neutrophil and B16 melanoma cell recruitment by rapidly influencing endothelial cell focal adhesion dynamics and junctional opening. Recently, we found that FAK related non-kinase (FRNK), a protein that is often used as a FAK dominant negative, blocked eosinophil transmigration by preventing the transcription of vascular cell adhesion molecule-1 (VCAM-1) and eotaxin-3 (CCL26). Surprisingly, the blocking occurred even in the absence of endogenous FAK. To better understand the role of FAK in leukocyte recruitment, we used a FAK-specific inhibitor (PF-573228) and determined the effect on IL-4 induced eosinophil recruitment in vitro and in vivo. PF-573228 prevented the expression of VCAM-1 and CCL26 expression in IL-4-stimulated human endothelial cells in vitro. As a result, eosinophil adhesion and transmigration were blocked. PF-572338 also prevented IL-4-induced VCAM-1 expression in vivo. Using brightfield intravital microscopy, we found that PF-573228 decreased leukocyte rolling flux, adhesion, and emigration. We specifically examined eosinophil recruitment in vivo by using an eosinophil-GFP reporter mouse and found PF-573228 attenuated eosinophil emigration. This study reveals that a FAK inhibitor influences inflammation through its action on eosinophil recruitment. ©2018 Society for Leukocyte Biology.

Comparison of Toxocariasis Frequency in Hyper- eosinophilic and Non-Eosinophilic Individuals Referred to Abadan Health Centers

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Sharif Maraghi

2014-07-01

Full Text Available Background: Toxocariasis is a zoonotic helminthic infection of humans and animals caused by the larvae of intestinal parasites of dogs and cats (Toxocara canis and Toxocara cati, respectively. These nematodes develop in to their adult stage in the intestines of cats and dogs. Three clinical entities have been recognized in humans; visceral larva migrans, ocular larva migrans and covert toxocariasis. Eosinophilia is a common finding in infected patients Objectives: In this study the frequency of toxocariasis in eosinophilic and non-eosinophilic individuals referred to the laboratory of Abadan health centers was compared. Materials and Methods: Serum samples were collected from individuals attending the laboratory of health centers for any medical problem and were tested for complet blood count (CBC. The samples of patients were divided in to two groups, those with more than 10% peripheral eosinophils, as the eosinophilic group (n = 54 and those with normal eosinophils (0-3% as the non-eosinophilic group (n = 54. Samples were examined for anti-oxocara IgG by the enzyme linked immunosorbent assay (ELISA and confirmed western blotting. Results: Anti-oxocara IgG was detected in the sera of six (11.11% cases from the eosinophilic group and two (3.7% of the non-eosinophilic group by the ELISA method, but all had negative results for the western blot analysis. Conclusions: The results of this study indicated that the eosinophilic individuals might beexposed to other helminthic infections or allergic agents. Further studies are required with more samples with different ages and occupations.

A case of cocaine-induced eosinophilic pneumonia: Case report and review of the literature

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Felix Reyes, MD

Full Text Available Cocaine is a commonly abused recreational drug in the United States. An adult man developed non-specific pleuritic chest pain, pharyngitis and odynophagia after inhaling cocaine. Initial laboratory results revealed eosinophilia. Bronchoalveolar lavage also showed eosinophilia in the lavage fluid. These findings suggested the diagnosis of eosinophilic pneumonia. Chest imaging revealed scattered bilateral opacities and interstitial infiltrates. After initiation of systemic corticosteroids, the patient reported symptomatic resolution and radiographic clearance was achieved at 2 months follow up.

Humoral immunity provides resident intestinal eosinophils access to luminal antigen via eosinophil-expressed low affinity Fc gamma receptors

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Smith, Kalmia M.; Rahman, Raiann S.; Spencer, Lisa A.

2016-01-01

Eosinophils are native to the healthy gastrointestinal tract, and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g. food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct antigen engagement elicits eosinophil effector functions including degranulation and antigen presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food antigens by a columnar epithelium might similarly engage food antigens. Using an intestinal ligated loop model in mice, here we determined that resident intestinal eosinophils acquire antigen from the lumen of antigen-sensitized but not naïve mice in vivo. Antigen acquisition was immunoglobulin-dependent; intestinal eosinophils were unable to acquire antigen in sensitized immunoglobulin-deficient mice, and passive immunization with immune serum or antigen-specific IgG was sufficient to enable intestinal eosinophils in otherwise naïve mice to acquire antigen in vivo. Intestinal eosinophils expressed low affinity IgG receptors, and the activating receptor FcγRIII was necessary for immunoglobulin-mediated acquisition of antigens by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food antigens in sensitized mice via FcγRIII antigen focusing, and may therefore participate in antigen-driven secondary immune responses to oral antigens. PMID:27683752

Humoral Immunity Provides Resident Intestinal Eosinophils Access to Luminal Antigen via Eosinophil-Expressed Low-Affinity Fcγ Receptors.

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Smith, Kalmia M; Rahman, Raiann S; Spencer, Lisa A

2016-11-01

Eosinophils are native to the healthy gastrointestinal tract and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g., food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct Ag engagement elicits eosinophil effector functions, including degranulation and Ag presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food Ags by a columnar epithelium might similarly engage food Ags. Using an intestinal ligated loop model in mice, in this study we determined that resident intestinal eosinophils acquire Ag from the lumen of Ag-sensitized but not naive mice in vivo. Ag acquisition was Ig-dependent; intestinal eosinophils were unable to acquire Ag in sensitized Ig-deficient mice, and passive immunization with immune serum or Ag-specific IgG was sufficient to enable intestinal eosinophils in otherwise naive mice to acquire Ag in vivo. Intestinal eosinophils expressed low-affinity IgG receptors, and the activating receptor FcγRIII was necessary for Ig-mediated acquisition of Ags by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food Ags in sensitized mice via FcγRIII Ag focusing and that they may therefore participate in Ag-driven secondary immune responses to oral Ags. Copyright © 2016 by The American Association of Immunologists, Inc.

Endogenous secreted phospholipase A2 group X regulates cysteinyl leukotrienes synthesis by human eosinophils.

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Hallstrand, Teal S; Lai, Ying; Hooper, Kathryn A; Oslund, Rob C; Altemeier, William A; Matute-Bello, Gustavo; Gelb, Michael H

2016-01-01

Phospholipase A2s mediate the rate-limiting step in the formation of eicosanoids such as cysteinyl leukotrienes (CysLTs). Group IVA cytosolic PLA2α (cPLA2α) is thought to be the dominant PLA2 in eosinophils; however, eosinophils also have secreted PLA2 (sPLA2) activity that has not been fully defined. To examine the expression of sPLA2 group X (sPLA2-X) in eosinophils, the participation of sPLA2-X in the formation of CysLTs, and the mechanism by which sPLA2-X initiates the synthesis of CysLTs in eosinophils. Peripheral blood eosinophils were obtained from volunteers with asthma and/or allergy. A rabbit polyclonal anti-sPLA2-X antibody identified sPLA2-X by Western blot. We used confocal microscopy to colocalize the sPLA2-X to intracellular structures. An inhibitor of sPLA2-X (ROC-0929) that does not inhibit other mammalian sPLA2s, as well as inhibitors of the mitogen-activated kinase cascade (MAPK) and cPLA2α, was used to examine the mechanism of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-mediated formation of CysLT. Eosinophils express the mammalian sPLA2-X gene (PLA2G10). The sPLA2-X protein is located in the endoplasmic reticulum, golgi, and granules of eosinophils and moves to the granules and lipid bodies during fMLP-mediated activation. Selective sPLA2-X inhibition attenuated the fMLP-mediated release of arachidonic acid and CysLT formation by eosinophils. Inhibitors of p38, extracellular-signal-regulated kinases 1/2 (p44/42 MAPK), c-Jun N-terminal kinase, and cPLA2α also attenuated the fMLP-mediated formation of CysLT. The sPLA2-X inhibitor reduced the phosphorylation of p38 and extracellular-signal-regulated kinases 1/2 (p44/42 MAPK) as well as cPLA2α during cellular activation, indicating that sPLA2-X is involved in activating the MAPK cascade leading to the formation of CysLT via cPLA2α. We further demonstrate that sPLA2-X is activated before secretion from the cell during activation. Short-term priming with IL-13 and TNF/IL-1β increased the

INFLAMMATORY INFILTRATION IN THE GASTRIC MUCOSA OF PATIENTS WITH EPSTEIN-BARR VIRUS-ASSOCIATED GASTRIC DYSPLASIA AND CANCER

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М. V. Vusik

2014-01-01

Full Text Available Characteristics of inflammatory infiltrate in the gastric mucosa of patients with gastric dysplasia (n=56 and gastric cancer (n=50 with different levels of humoral immune response to Epstein-Barr virus (EBV and EBV viral load were studied. In patients with dysplasia of the gastric mucosa, the increase in antibody titers to VCA IgG leaded to a significant decrease in the level of lymphocytes, neutrophils and macrophages and an increase in the number of eosinophils and plasma cells. When the levels of IgA to viral capsid antigen (VCA and IgG to EBV early antigens (EA were increased, the number of neutrophils in the composition of the cellular infiltrate was significantly decreased. In gastric cancer patients with different levels of humoral immune response to EBV, the number of plasma cells and eosinophils in the inflammatory infiltrate of the tumor was decreased when increasing the titers of IgG to VCA and IgA to VCA. When VCA/IgA titer was high, the number of neutrophils in a tumor was decreased and the proportion of macrophages was slightly increased. The data obtained can serve as additional criteria for indentifying markers for viral infection of the gastric mucosa.

Eosinophils in vasculitis: characteristics and roles in pathogenesis

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Khoury, Paneez; Grayson, Peter C.; Klion, Amy D.

2016-01-01

Eosinophils are multifunctional granular leukocytes that are implicated in the pathogenesis of a wide variety of disorders, including asthma, helminth infection, and rare hypereosinophilic syndromes. Although peripheral and tissue eosinophilia can be a feature of many types of small-vessel and medium-vessel vasculitis, the role of eosinophils has been best studied in eosinophilic granulomatosis with polyangiitis (EGPA), where eosinophils are a characteristic finding in all three clinical stages of the disorder. Whereas numerous studies have demonstrated an association between the presence of eosinophils and markers of eosinophil activation in the blood and tissues of patients with EGPA, the precise role of eosinophils in disease pathogenesis has been difficult to ascertain owing to the complexity of the disease process. In this regard, results of clinical trials using novel agents that specifically target eosinophils are providing the first direct evidence of a central role of eosinophils in EGPA. This Review focuses on the aspects of eosinophil biology most relevant to the pathogenesis of vasculitis and provides an update of current knowledge regarding the role of eosinophils in EGPA and other vasculitides. PMID:25003763

Activation states of blood eosinophils in asthma

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Johansson, Mats W.

2014-01-01

Asthma is characterized by airway inflammation rich in eosinophils. Airway eosinophilia is associated with exacerbations and has been suggested to play a role in airway remodeling. Recruitment of eosinophils from the circulation requires that blood eosinophils become activated, leading to their arrest on the endothelium and extravasation. Circulating eosinophils can be envisioned as potentially being in different activation states, including non-activated, pre-activated or “primed”, or fully activated. In addition, the circulation can potentially be deficient of pre-activated or activated eosinophils, because such cells have marginated on activated endothelium or extravasated into the tissue. A number of eosinophil-surface proteins, including CD69, L-selectin, intercellular adhesion molecule-1 (ICAM-1, CD54), CD44, P-selectin glycoprotein ligand-1 (PSGL-1, CD162), cytokine receptors, Fc receptors, integrins including αM integrin (CD11b), and activated conformations of Fc receptors and integrins have been proposed to report cell activation. Variation in eosinophil activation states may be associated with asthma activity. Eosinophil-surface proteins proposed to be activation markers, with a particular focus on integrins, and evidence for associations between activation states of blood eosinophils and features of asthma are reviewed here. Partial activation of β1 and β2 integrins on blood eosinophils, reported by monoclonal antibodies (mAb) N29 and KIM-127, is associated with impaired pulmonary function and airway eosinophilia, respectively, in non-severe asthma. The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre-activated cells, in severe disease. PMID:24552191

Involvement of both protein kinase C and G proteins in superoxide production after IgE triggering in guinea pig eosinophils

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Toshiya Aizawa

1997-01-01

Full Text Available To study the function and mechanism of eosinophils via the low affinity IgE receptor (FceRII, we examined the production of 02 metabolites by measuring the luminol-dependent chemiluminescence (LDCL response and the generation of cysteinyl leukotrienes. Eosinophils obtained from guinea pig peritoneal fluid sensitized with horse serum were purified. Luminol-dependent chemiluminescence was induced by stimulation with monoclonal anti-CD23 antibody, but not by mouse serum (controls. The mean (±SEM value of LDCL was 20.6±1.3X103 c.p.m. This reaction consisted of an initial rapid phase and a propagation phase and ended within lOmin. Guinea pig eosinophils were histochemically stained with monoclonal anti-CD23 antibody. The major product generated in the LDCL response was superoxide, as determined by the measurement of superoxide by cytochrome c reduction and the complete inhibitory effect of superoxide dismutase on the LDCL response. Pretreatment with either pertussis toxin or cholera toxin inhibited the LDCL reaction. Depletion of bivalent ions by EDTA inhibited this response and the protein kinase C inhibitor D-sphingosin inhibited both 1-oleoyl-2-acetyl-glycerol-induced and FcϵRII-mediated LDCL. These findings suggest that the NADPH-protein kinase C pathway may be involved in the FceRII-mediated LDCL response in guinea pig eosinophils.

Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma

NARCIS (Netherlands)

Meijer, RJ; Postma, DS; Kauffman, HF; Arends, LR; Koeter, GH; Kerstjens, HAM

Background There is a large variability in clinical response to corticosteroid treatment in patients with asthma. Several markers of inflammation like eosinophils and eosinophil cationic protein (ECP), as well as exhaled nitric oxide (NO), are good candidates to predict clinical response. Aim We

Production of monoclonal antibodies reactive with ovine eosinophils

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Meeusen Els NT

2007-09-01

Full Text Available Abstract Background There is strong evidence implicating eosinophils in host defence against parasites as well as allergic disease pathologies. However, a lack of reagents such as monoclonal antibodies (mAbs specific for eosinophils has made it difficult to confirm the functional role of eosinophils in such disease conditions. Using an established mammary model of allergic inflammation in sheep, large numbers of inflammatory cells enriched for eosinophils were collected from parasite-stimulated mammary glands and used for the generation of mAbs against ovine eosinophils. Results A panel of mAbs was raised against ovine eosinophils of which two were shown to be highly specific for eosinophils. The reactivity of mAbs 3.252 and 1.2 identified eosinophils from various cell and tissue preparations with no detectable reactivity on cells of myeloid or lymphoid lineage, tissue mast cells, dendritic cells, epithelial cells or other connective tissues. Two other mAbs generated in this study (mAbs 4.4 and 4.10 were found to have reactivity for both eosinophils and neutrophils. Conclusion This study describes the production of new reagents to identify eosinophils (as well as granulocytes in sheep that will be useful in studying the role of eosinophils in disease pathologies in parasite and allergy models.

Eosinophils: The unsung heroes in cancer?

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Varricchi, Gilda; Galdiero, Maria Rosaria; Loffredo, Stefania; Lucarini, Valeria; Marone, Giancarlo; Mattei, Fabrizio; Marone, Gianni; Schiavoni, Giovanna

2018-01-01

Prolonged low-grade inflammation or smoldering inflammation is a hallmark of a cancer. Eosinophils are components of the immune microenvironment that modulates tumor initiation and progression. Although canonically associated with a detrimental role in allergic disorders, these cells can induce a protective immune response against helminthes, viral and bacterial pathogens. Eosinophils are a source of anti-tumorigenic (e.g., TNF-α, granzyme, cationic proteins, and IL-18) and protumorigenic molecules (e.g., pro-angiogenic factors) depending on the milieu. In several neoplasias (e.g., melanoma, gastric, colorectal, oral and prostate cancer) eosinophils play an anti-tumorigenic role, in others (e.g., Hodgkin's lymphoma, cervical carcinoma) have been linked to poor prognosis, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of eosinophils and their mediators could be cancer-dependent. The microlocalization (e.g., peritumoral vs intratumoral) of eosinophils could be another important aspect in the initiation/progression of solid and hematological tumors. Increasing evidence in experimental models indicates that activation/recruitment of eosinophils could represent a new therapeutic strategy for certain tumors (e.g., melanoma). Many unanswered questions should be addressed before we understand whether eosinophils are an ally, adversary or neutral bystanders in different types of human cancers.

Cisplatin-Induced Eosinophilic Pneumonia

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Hideharu Ideguchi

2014-01-01

Full Text Available A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.

A comparison of the inhibitory activity of selective PDE4 inhibitors on eosinophil recruitment in guinea pig skin

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Mauro M Teixeira

1997-12-01

Full Text Available The elevation of intracellular cyclic AMP by phosphodiesterase (PDE4 inhibitors in eosinophils is associated with inhibition of the activation and recruitment of these cells. We have previously shown that systemic treatment with the PDE4 inhibitor rolipram effectively inhibt eosinophil migration in guinea pig skin. In the present study we compare the oral potency and efficacy of the PDE4 inhibitors rolipram, RP 73401 and CDP 840 on allergic and PAF-induced eosinophil recruitment. Rolipram and RP 73401 were equally effective and potent when given by the oral route and much more active than the PDE4 inhibitor CDP 840. We suggest that this guinea pig model of allergic and mediator-induced eosinophil recruitment is both a sensitive and simple tool to test the efficacy and potency of PDE4 inhibitors in vivo.

Eosinophils mediate protective immunity against secondary nematode infection.

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Huang, Lu; Gebreselassie, Nebiat G; Gagliardo, Lucille F; Ruyechan, Maura C; Luber, Kierstin L; Lee, Nancy A; Lee, James J; Appleton, Judith A

2015-01-01

Eosinophils are versatile cells that regulate innate and adaptive immunity, influence metabolism and tissue repair, and contribute to allergic lung disease. Within the context of immunity to parasitic worm infections, eosinophils are prominent yet highly varied in function. We have shown previously that when mice undergo primary infection with the parasitic nematode Trichinella spiralis, eosinophils play an important immune regulatory role that promotes larval growth and survival in skeletal muscle. In this study, we aimed to address the function of eosinophils in secondary infection with T. spiralis. By infecting eosinophil-ablated mice, we found that eosinophils are dispensable for immunity that clears adult worms or controls fecundity in secondary infection. In contrast, eosinophil ablation had a pronounced effect on secondary infection of skeletal muscle by migratory newborn larvae. Restoring eosinophils to previously infected, ablated mice caused them to limit muscle larvae burdens. Passive immunization of naive, ablated mice with sera or Ig from infected donors, together with transfer of eosinophils, served to limit the number of newborn larvae that migrated in tissue and colonized skeletal muscle. Results from these in vivo studies are consistent with earlier findings that eosinophils bind to larvae in the presence of Abs in vitro. Although our previous findings showed that eosinophils protect the parasite in primary infection, these new data show that eosinophils protect the host in secondary infection. Copyright © 2014 by The American Association of Immunologists, Inc.

IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration.

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Johansson, M W; Khanna, M; Bortnov, V; Annis, D S; Nguyen, C L; Mosher, D F

2017-10-01

IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod," which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators. Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin. Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed. After 10 minutes in the presence of IL-5, adherent eosinophils were polarized with PSGL-1 at the nucleopod tip and F-actin distributed diffusely at the opposite end. After 30-60 minutes, the nucleopod had dissipated such that PSGL-1 was localized in a crescent or ring away from the cell periphery, and F-actin was found in podosome-like structures. The periostin layer, detected with monoclonal antibody Stiny-1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase previously implicated in asthma pathogenesis. ADAM8 was not found in podosome-like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti-ADAM8 inhibited migration of IL-5-stimulated eosinophils on periostin. Migrating IL-5-activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny-1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate

Regulatory Eosinophils Suppress T Cells Partly through Galectin-10.

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Lingblom, Christine; Andersson, Jennie; Andersson, Kerstin; Wennerås, Christine

2017-06-15

Eosinophils have the capacity to regulate the function of T cell subsets. Our aim was to test the hypothesis of the existence of a regulatory subset of eosinophils. Human eosinophils were incubated with T cells that were stimulated with allogeneic leukocytes or CD3/CD28 cross-linking. After 2 d of coculture, 11% of the eosinophils gained CD16 expression. A CD16 hi subset of eosinophils, encompassing 1-5% of all eosinophils, was also identified in the blood of healthy subjects. FACS sorting showed that these CD16 hi eosinophils were significantly stronger suppressors of T cell proliferation than were conventional CD16 neg eosinophils. Human eosinophils contain stores of the immunoregulatory protein galectin-10. We found that Ab-mediated neutralization of galectin-10 partially abrogated the suppressive function of the eosinophils. Moreover, recombinant galectin-10 by itself was able to suppress T cell proliferation. Finally, we detected galectin-10-containing immune synapses between eosinophils and lymphocytes. To conclude, we describe a subset of suppressive eosinophils expressing CD16 that may escape detection because CD16-based negative selection is the standard procedure for the isolation of human eosinophils. Moreover, we show that galectin-10 functions as a T cell-suppressive molecule in eosinophils. Copyright © 2017 by The American Association of Immunologists, Inc.

The effect of tributyltin on human eosinophilic [correction of eosinophylic] leukemia EoL-1 cells.

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Sroka, Jolanta; Włosiak, Przemysław; Wilk, Anna; Antonik, Justyna; Czyz, Jarosław; Madeja, Zbigniew

2008-01-01

Organotin compounds are chemicals that are widely used in industry and agriculture as plastic stabilizers, catalysts and biocides. Many of them, including tributyltin (TBT), have been detected in human food and, as a consequence, detectable levels have been found in human blood. As organotin compounds were shown to possess immunotoxic activity, we focused our attention on the effect of TBT on the basic determinants of the function of eosinophils, i.e. cell adhesiveness and motility. We used human eosinophylic leukemia EoL-1 cells, a common in vitro cellular model of human eosinophils. Here, we demonstrate that TBT causes a dose-dependent decrease in the viability of EoL-1 cells. When administered at sub-lethal concentrations, TBT significantly decreases the adhesion of EoL-1 cells to human fibroblasts (HSFs) and inhibits their migration on fibroblast surfaces. Since the basic function of eosinophils is to invade inflamed tissues, our results indicate that TBT, and possibly other organotin compounds, may affect major cellular properties involved in the determination of in vivo eosinophil function.

Human eosinophils are direct targets to nanoparticles: Zinc oxide nanoparticles (ZnO) delay apoptosis and increase the production of the pro-inflammatory cytokines IL-1β and IL-8.

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Silva, Luis Rafael; Girard, Denis

2016-09-30

Zinc oxide NPs (ZnO) have been recently proposed as novel candidates for the treatment of allergic inflammatory diseases. Paradoxically, recent data suggested that ZnO could cause eosinophilic airway inflammation in rodents. Despite the above observations, there are currently no studies reporting direct interaction between a given NP and human eosinophils themselves. In this study, freshly isolated human eosinophils were incubated with ZnO and several cellular functions were studied. We found that ZnO delay human eosinophil apoptosis, partially by inhibiting caspases and by preventing caspase-4 and Bcl-xL degradation. ZnO do not induce production of reactive oxygen species but increase de novo protein synthesis. In addition, ZnO were found to increase the production of the proinflammatory IL-1β and IL-8 cytokines. Using a pharmacological approach, we demonstrated that inhibition of caspase-1 reversed the ability of ZnO to induce IL-1β and IL-8 production, whereas inhibition of caspase-4 only reversed that of IL-8. Our results indicate the necessity of conducting studies to determine the potential of using NP as nanotherapies, particularly in diseases in which eosinophils may be involved. We conclude that, indeed, human eosinophils represent potential new direct targets to NPs, ZnO in the present case. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

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D. Carlos

2011-04-01

Full Text Available It is well known that eosinophilia is a key pathogenetic component of toxocariasis. The objective of the present study was to determine if there is an association between peritoneal and blood eosinophil influx, mast cell hyperplasia and leukotriene B4 (LTB4 production after Toxocara canis infection. Oral inoculation of 56-day-old Wistar rats (N = 5-7 per group with 1000 embryonated eggs containing third-stage (L3 T. canis larvae led to a robust accumulation of total leukocytes in blood beginning on day 3 and peaking on day 18, mainly characterized by eosinophils and accompanied by higher serum LTB4 levels. At that time, we also noted increased eosinophil numbers in the peritoneal cavity. In addition, we observed increased peritoneal mast cell number in the peritoneal cavity, which correlated with the time course of eosinophilia during toxocariasis. We also demonstrated that mast cell hyperplasia in the intestines and lungs began soon after the T. canis larvae migrated to these compartments, reaching maximal levels on day 24, which correlated with the complete elimination of the parasite. Therefore, mast cells appear to be involved in peritoneal and blood eosinophil infiltration through an LTB4-dependent mechanism following T. canis infection in rats. Our data also demonstrate a tight association between larval migratory stages and intestinal and pulmonary mast cell hyperplasia in the toxocariasis model.

Human and Mouse Eosinophils Have Antiviral Activity against Parainfluenza Virus.

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Drake, Matthew G; Bivins-Smith, Elizabeth R; Proskocil, Becky J; Nie, Zhenying; Scott, Gregory D; Lee, James J; Lee, Nancy A; Fryer, Allison D; Jacoby, David B

2016-09-01

Respiratory viruses cause asthma exacerbations. Because eosinophils are the prominent leukocytes in the airways of 60-70% of patients with asthma, we evaluated the effects of eosinophils on a common respiratory virus, parainfluenza 1, in the lung. Eosinophils recruited to the airways of wild-type mice after ovalbumin sensitization and challenge significantly decreased parainfluenza virus RNA in the lungs 4 days after infection compared with nonsensitized animals. This antiviral effect was also seen in IL-5 transgenic mice with an abundance of airway eosinophils (NJ.1726) but was lost in transgenic eosinophil-deficient mice (PHIL) and in IL-5 transgenic mice crossed with eosinophil-deficient mice (NJ.1726-PHIL). Loss of the eosinophil granule protein eosinophil peroxidase, using eosinophil peroxidase-deficient transgenic mice, did not reduce eosinophils' antiviral effect. Eosinophil antiviral mechanisms were also explored in vitro. Isolated human eosinophils significantly reduced parainfluenza virus titers. This effect did not involve degradation of viral RNA by eosinophil granule RNases. However, eosinophils treated with a nitric oxide synthase inhibitor lost their antiviral activity, suggesting eosinophils attenuate viral infectivity through production of nitric oxide. Consequently, eosinophil nitric oxide production was measured with an intracellular fluorescent probe. Eosinophils produced nitric oxide in response to virus and to a synthetic agonist of the virus-sensing innate immune receptor, Toll-like receptor (TLR) 7. IFNγ increased expression of eosinophil TLR7 and potentiated TLR7-induced nitric oxide production. These results suggest that eosinophils promote viral clearance in the lung and contribute to innate immune responses against respiratory virus infections in humans.

Neither eosinophils nor neutrophils require ATG5-dependent autophagy for extracellular DNA trap formation.

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Germic, Nina; Stojkov, Darko; Oberson, Kevin; Yousefi, Shida; Simon, Hans-Uwe

2017-11-01

The importance of extracellular traps (ETs) in innate immunity is well established, but the molecular mechanisms responsible for their formation remain unclear and in scientific dispute. ETs have been defined as extracellular DNA scaffolds associated with the granule proteins of eosinophils or neutrophils. They are capable of killing bacteria extracellularly. Based mainly on results with phosphoinositide 3-kinase (PI3K) inhibitors such as 3-methyladenine (3-MA) and wortmannin, which are commonly used to inhibit autophagy, several groups have reported that autophagy is required for neutrophil extracellular trap (NET) formation. We decided to investigate this apparent dependence on autophagy for ET release and generated genetically modified mice that lack, specifically in eosinophils or neutrophils, autophagy-related 5 (Atg5), a gene encoding a protein essential for autophagosome formation. Interestingly, neither eosinophils nor neutrophils from Atg5-deficient mice exhibited abnormalities in ET formation upon physiological activation or exposure to low concentrations of PMA, although we could confirm that human and mouse eosinophils and neutrophils, after pre-treatment with inhibitors of class III PI3K, show a block both in reactive oxygen species (ROS) production and in ET formation. The so-called late autophagy inhibitors bafilomycin A1 and chloroquine, on the other hand, were without effect. These data indicate that ET formation occurs independently of autophagy and that the inhibition of ROS production and ET formation in the presence of 3-MA and wortmannin is probably owing to their additional ability to block the class I PI3Ks, which are involved in signalling cascades initiated by triggers of ET formation. © 2017 John Wiley & Sons Ltd.

Clinical characteristics of eosinophilic asthma exacerbations

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Bjerregaard, Asger; Laing, Ingrid A; Backer, Vibeke

2017-01-01

blood cell counts and a screening for common respiratory viruses and bacteria. An eosinophilic exacerbation (EE) was defined as having sputum eosinophils ≥ 3% and a non-eosinophilic exacerbation as NEE). RESULTS: A total of 47 patients were enrolled; 37 (79%) had successful sputum induction...... at baseline, of whom 43% had sputum eosinophils ≥3% (EE). Patients with EE had a significantly lower forced expiratory volume in 1 s (FEV1 ) % predicted (70.8%, P = 0.03) than patients with NEE (83.6%). Furthermore, EE patients were more likely to require supplemental oxygen during admission (63% vs 14%, P...... = 0.002). The prevalence of respiratory viruses was the same in EE and NEE patients (44% vs 52%, P = 0.60), as was bacterial infection (6% vs 14%, P = 0.44). Fractional expiratory nitric oxide (FeNO) correlated with sputum %-eosinophils (ρ = 0.57, P

Long-term follow-up in dogs with idiopathic eosinophilic bronchopneumopathy treated with inhaled steroid therapy.

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Canonne, A M; Bolen, G; Peeters, D; Billen, F; Clercx, C

2016-10-01

Treatment of canine idiopathic eosinophilic bronchopneumopathy mainly consists of long-term oral corticosteroid therapy. To avoid side effects, inhaled steroid therapy has been increasingly used but long-term clinical response and potential side effects are sparsely described. Description of clinical response and side effects with long-term fluticasone in dogs with eosinophilic bronchopneumopathy. Case series of dogs with eosinophilic bronchopneumopathy and treated with fluticasone monotherapy for at least 6 months. Clinical response and side effects assessed by physical examination, standardised questionnaire and ACTH (corticotropin) stimulation test. Eight dogs were treated for between 6 months and 5 years. Cough initially improved in all dogs; two dogs remained free of clinical signs, three were well controlled, but three showed severe relapse. Pituitary-adrenal axis inhibition occurred in two dogs treated with fluticasone monotherapy for more than 2 years; only one dog had clinical signs of iatrogenic hyperadrenocorticism. Fluticasone monotherapy allows initial improvement or remission in the majority of dogs but long-term treatment fails to resolve the cough in some individuals. In addition, such therapy may induce pituitary-adrenal axis inhibition. Prospective larger and randomised studies including both fluticasone and orally-treated dogs are needed to define the optimal treatment. © 2016 British Small Animal Veterinary Association.

Eosinophils in helminth infection: defenders and dupes

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Huang, Lu; Appleton, Judith A.

2016-01-01

Eosinophilia is a central feature of the host response to helminth infection. Larval stages of parasitic worms are killed in vitro by eosinophils in the presence of specific antibodies or complement. These findings established host defense as the paradigm for eosinophil function. Recently, studies in eosinophil-ablated mouse strains have revealed an expanded repertoire of immunoregulatory functions for this cell. Other reports document crucial roles for eosinophils in tissue homeostasis and metabolism, processes that are central to the establishment and maintenance of parasitic worms in their hosts. In this review, we summarize current understanding of the significance of eosinophils at the host-parasite interface, highlighting their distinct functions during primary and secondary exposure. PMID:27262918

Eosinophils: important players in humoral immunity.

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Berek, C

2016-01-01

Eosinophils perform numerous tasks. They are involved in inflammatory reactions associated with innate immune defence against parasitic infections and are also involved in pathological processes in response to allergens. Recently, however, it has become clear that eosinophils also play crucial non-inflammatory roles in the generation and maintenance of adaptive immune responses. Eosinophils, being a major source of the plasma cell survival factor APRIL (activation and proliferation-induced ligand), are essential not only for the long-term survival of plasma cells in the bone marrow, but also for the maintenance of these cells in the lamina propria which underlies the gut epithelium. At steady state under non-inflammatory conditions eosinophils are resident cells of the gastrointestinal tract, although only few are present in the major organized lymphoid tissue of the gut - the Peyer's patches (PP). Surprisingly, however, lack of eosinophils abolishes efficient class-switching of B cells to immunoglobulin (Ig)A in the germinal centres of PP. Thus, eosinophils are required to generate and to maintain mucosal IgA plasma cells, and as a consequence their absence leads to a marked reduction of IgA both in serum and in the gut-associated lymphoid tissues (GALT). Eosinophils thus have an essential part in long-term humoral immune protection, as they are crucial for the longevity of antibody-producing plasma cells in the bone marrow and, in addition, for gut immune homeostasis. © 2015 British Society for Immunology.

Eosinophils Contribute to Intestinal Inflammation via Chemoattractant Receptor-homologous Molecule Expressed on Th2 Cells, CRTH2, in Experimental Crohn's Disease.

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Radnai, Balázs; Sturm, Eva M; Stančić, Angela; Jandl, Katharina; Labocha, Sandra; Ferreirós, Nerea; Grill, Magdalena; Hasenoehrl, Carina; Gorkiewicz, Gregor; Marsche, Gunther; Heinemann, Ákos; Högenauer, Christoph; Schicho, Rudolf

2016-09-01

Prostaglandin [PG] D2 activates two receptors, DP and CRTH2. Antagonism of CRTH2 has been shown to promote anti-allergic and anti-inflammatory effects. We investigated whether CRTH2 may play a role in Crohn's disease [CD], focusing on eosinophils which are widely present in the inflamed mucosa of CD patients and express both receptors. Using the 2,4,6-trinitrobenzenesulfonic acid [TNBS]-induced colitis model, involvement of CRTH2 in colitis was investigated by pharmacological antagonism, immunohistochemistry, Western blotting, immunoassay, and leukocyte recruitment. Chemotactic assays were performed with isolated human eosinophils. Biopsies and serum samples of CD patients were examined for presence of CRTH2 and ligands, respectively. High amounts of CRTH2-positive cells, including eosinophils, are present in the colonic mucosa of mice with TNBS colitis and in human CD. The CRTH2 antagonist OC-459, but not the DP antagonist MK0524, reduced inflammation scores and decreased TNF-α, IL-1β, and IL-6 as compared with control mice. OC-459 inhibited recruitment of eosinophils into the colon and also inhibited CRTH2-induced chemotaxis of human eosinophils in vitro. Eosinophil-depleted ΔdblGATA knockout mice were less sensitive to TNBS-induced colitis, whereas IL-5 transgenic mice with lifelong eosinophilia were more severely affected than wild types. In addition, we show that serum levels of PGD2 and Δ(12)-PGJ2 were increased in CD patients as compared with control individuals. CRTH2 plays a pro-inflammatory role in TNBS-induced colitis. Eosinophils contribute to the severity of the inflammation, which is improved by a selective CRTH2 antagonist. CRTH2 may, therefore, represent an important target in the pharmacotherapy of CD. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Facial and extrafacial eosinophilic pustular folliculitis: a clinical and histopathological comparative study.

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Lee, W J; Won, K H; Won, C H; Chang, S E; Choi, J H; Moon, K C; Lee, M W

2014-05-01

Although more than 300 cases of eosinophilic pustular folliculitis (EPF) have been reported to date, differences in clinicohistopathological findings among affected sites have not yet been evaluated. To evaluate differences in the clinical and histopathological features of facial and extrafacial EPF. Forty-six patients diagnosed with EPF were classified into those with facial and extrafacial disease according to the affected site. Clinical and histopathological characteristics were retrospectively compared, using all data available in the patient medical records. There were no significant between-group differences in subject ages at presentation, but a male predominance was observed in the extrafacial group. In addition, immunosuppression-associated type EPF was more common in the extrafacial group. Eruptions of plaques with an annular appearance were more common in the facial group. Histologically, perifollicular infiltration of eosinophils occurred more frequently in the facial group, whereas perivascular patterns occurred more frequently in the extrafacial group. Follicular mucinosis and exocytosis of inflammatory cells in the hair follicles were strongly associated with facial EPF. The clinical and histopathological characteristics of patients with facial and extrafacial EPF differ, suggesting the involvement of different pathogenic processes in the development of EPF at different sites. © 2013 British Association of Dermatologists.

Leukemia -- Eosinophilic

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... social workers, and patient advocates. Cancer.Net Guide Leukemia - Eosinophilic Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

Evidence for eosinophil degranulation in acute appendicitis

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Santosh G

2008-04-01

Full Text Available Finding of increased numbers of eosinophils in the muscle in cases of acute appendicitis has led to the hypothesis that it may have an allergic origin. This study aimed to measure the eosinophil degranulation resulting in a rise in the serum of eosinophil granule proteins that would be expected in such cases. The levels of serum eosinophil cationic protein (ECP measured by chemiluminescence assay in acute appendicitis were compared, with those of appropriate controls. Mean (95% CI serum ECP (µg/L levels were: acute appendicitis 45.3 (27.7-63.0; normal appendix 22.7 (16.0-29.3; asthma 24.2 (4.6-43.8; and healthy volunteers 13.2 (8.3-18.1. In cases of acute appendicitis, there is an inverse relationship between duration of symptoms and serum ECP. However, this was not statistically significant. Significant local eosinophil activation and degranulation occurs in acute appendicitis, enough to cause a rise in serum levels of eosinophil chemotactic protein

Imipenem/cilastatin-induced acute eosinophilic pneumonia.

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Foong, Kap Sum; Lee, Ashley; Pekez, Marijeta; Bin, Wei

2016-03-04

Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute eosinophilic pneumonia. In this study, we present a case of imipenem/cilastatin-induced acute eosinophilic pneumonia. The patient presented with fever, acute hypoxic respiratory distress, and diffuse ground-glass opacities on the chest CT a day after the initiation of imipenem/cilastatin. Patient also developed peripheral eosinophilia. A reinstitution of imipenem/cilastatin resulted in recurrence of the signs and symptoms. A bronchoscopy with bronchoalveolar lavage showed 780 nucleated cells/mm(3) with 15% eosinophil. The patient's clinical condition improved significantly after the discontinuation of imipenem/cilastatin therapy and the treatment with corticosteroid. 2016 BMJ Publishing Group Ltd.

Eosinophils from Murine Lamina Propria Induce Differentiation of Naïve T Cells into Regulatory T Cells via TGF-β1 and Retinoic Acid.

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Hong-Hu Chen

Full Text Available Treg cells play a crucial role in immune tolerance, but mechanisms that induce Treg cells are poorly understood. We here have described eosinophils in lamina propria (LP that displayed high aldehyde dehydrogenase (ALDH activity, a rate-limiting step during all-trans retinoic acid (ATRA synthesis, and expressed TGF-β1 mRNA and high levels of ATRA. Co-incubation assay confirmed that LP eosinophils induced the differentiation of naïve T cells into Treg cells. Differentiation promoted by LP eosinophils were inhibited by blocked either TGF-β1 or ATRA. Peripheral blood (PB eosinophils did not produce ATRA and could not induce Treg differentiation. These data identifies LP eosinophils as effective inducers of Treg cell differentiation through a mechanism dependent on TGF-β1 and ATRA.

Eosinophils: changing perspectives in health and disease

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Rosenberg, Helene F.; Dyer, Kimberly D.; Foster, Paul S.

2015-01-01

Eosinophils have been traditionally perceived as largely end-stage, cytotoxic effector cells. Recent studies have profoundly altered this simplistic view of eosinophils and their function. New insights into the molecular basis of development, trafficking and degranulation of eosinophils have provided a better understanding of the role of these cells in promoting homeostasis through their immunomodulatory functions. Likewise, recent developments have generated a more sophisticated view of how eosinophils contribute to the pathogenesis of disease, including asthma and primary hypereosinophilic syndromes, and also a more complete appreciation of their activities in parasitic infection. PMID:23154224

Esophageal involvement in eosinophilic gastroenteritis

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Matzinger, M A; Daneman, A

1983-02-01

The radiologic appearance of esophageal involvement due to eosinophilic gastroenteritis in a 15-year-old boy is presented. The lower two thirds of the esophagus was narrowed and the peristalsis diminished. The mucosa appeared smooth. This is the fourth reported case of esophageal involvement in eosinophilic gastroenteritis.

Eosinophils in mucosal immune responses

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Travers, J; Rothenberg, M E

2015-01-01

Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

Genetics Home Reference: PDGFRB-associated chronic eosinophilic leukemia

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... associated chronic eosinophilic leukemia PDGFRB-associated chronic eosinophilic leukemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description PDGFRB -associated chronic eosinophilic leukemia is a type of cancer of blood-forming ...

Elevations in vascular markers and eosinophils in chronic spontaneous urticarial weals with low-level persistence in uninvolved skin

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Kay, AB; Ying, S; Ardelean, E; Mlynek, A; Kita, H; Clark, P; Maurer, M

2014-01-01

Background In chronic spontaneous urticaria (CSU) mast cell activation together with inflammatory changes in the skin are well documented and may play an important role in mechanisms of tissue oedema. Objectives To confirm and extend these observations by measuring microvascular markers, leucocytes and mast cell numbers in lesional and uninvolved skin and to compare findings with a control group. Methods Paired biopsies (one from 4–8-h spontaneous weals and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects and studied using immunohistochemistry and confocal microscopy using the lectin Ulex europaeus agglutinin 1 (UEA-1). Results Lesional skin in CSU contained significantly more CD31+ endothelial cells; CD31+ blood vessels, neutrophils, eosinophils, basophils and macrophages; and CD3+ T cells than nonlesional skin. Increased vascularity was confirmed by confocal imaging using the lectin UEA-1. Uninvolved skin from CSU contained significantly more CD31+ endothelial cells, CD31+ blood vessels and eosinophils compared with the control subjects. There was a threefold increase in mast cell numbers when CSU was compared with controls but no difference was observed between lesional and uninvolved skin. Conclusions Increased vascular markers together with eosinophil and neutrophil infiltration are features of lesional skin in CSU and might contribute to tissue oedema. Eosinophils and microvascular changes persist in uninvolved skin, which, together with increased mast cells, suggests that nonlesional skin is primed for further wealing. PMID:24665899

Human versus mouse eosinophils: "that which we call an eosinophil, by any other name would stain as red".

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Lee, James J; Jacobsen, Elizabeth A; Ochkur, Sergei I; McGarry, Michael P; Condjella, Rachel M; Doyle, Alfred D; Luo, Huijun; Zellner, Katie R; Protheroe, Cheryl A; Willetts, Lian; Lesuer, William E; Colbert, Dana C; Helmers, Richard A; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A

2012-09-01

The respective life histories of human subjects and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiologic pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils, their effector functions, or both. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide experimental details comparing and contrasting eosinophils and eosinophil effector functions in human subjects versus mice. In particular, our review will provide a summation and an easy-to-use reference guide to important studies demonstrating that although differences exist, more often than not, their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function but instead species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN). Detection by enzyme-linked immunosorbent assay and purification from normal human urine

DEFF Research Database (Denmark)

Reimert, C M; Minuva, U; Kharazmi, A

1991-01-01

Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN) is one of the cationic proteins found in the granules of the human eosinophilic granulocytes. EPX was purified from extracts of granules isolated from blood buffy coat cells of healthy donors. Polyclonal anti-EPX antibodies were...

EOSINOPHILS: MULTIFACETED BIOLOGIC PROPERTIES AND ROLES IN HEALTH AND DISEASE

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Kita, Hirohito

2011-01-01

Summary Eosinophils are leukocytes resident in mucosal tissues. During Th2-type inflammation, eosinophils are recruited from bone marrow and blood to the sites of immune response. While eosinophils have been considered end-stage cells involved in host protection against parasite infection and immunopathology in hypersensitivity disease, recent studies changed this perspective. Eosinophils are now considered multifunctional leukocytes involved in tissue homeostasis, modulation of adaptive immune responses, and innate immunity to certain microbes. Eosinophils are capable of producing immunoregulatory cytokines and are actively involved in regulation of Th2-type immune responses. However, such new information does not preclude earlier observations showing that eosinophils, in particular human eosinophils, are also effector cells with pro-inflammatory and destructive capabilities. Eosinophils with activation phenotypes are observed in biological specimens from patients with disease, and deposition of eosinophil products is readily seen in the affected tissues from these patients. Therefore, it would be reasonable to consider the eosinophil a multifaceted leukocyte that contributes to various physiological and pathological processes depending on their location and activation status. This review summarizes the emerging concept of the multifaceted immunobiology of eosinophils and discusses the roles of eosinophils in health and disease and the challenges and perspectives in the field. PMID:21682744

Blood eosinophil levels as a biomarker in COPD.

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Brusselle, Guy; Pavord, Ian D; Landis, Sarah; Pascoe, Steven; Lettis, Sally; Morjaria, Nikhil; Barnes, Neil; Hilton, Emma

2018-05-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder and patients respond differently to treatment. Blood eosinophils are a potential biomarker to stratify patient subsets for COPD therapy. We reviewed the value of blood eosinophils in predicting exacerbation risk and response to corticosteroid treatment in the available literature (PubMed articles in English; keywords: "COPD" and "eosinophil"; published prior to May 2017). Overall, clinical data suggest that in patients with a history of COPD exacerbations, a higher blood eosinophil count predicts an increased risk of future exacerbations and is associated with improved response to treatment with inhaled corticosteroids (in combination with long-acting bronchodilator[s]). Blood eosinophils are therefore a promising biomarker for phenotyping patients with COPD, although prospective studies are needed to assess blood eosinophils as a biomarker of corticosteroid response for this. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human vs. Mouse Eosinophils: “That which we call an eosinophil, by any other name would stain as red”

Science.gov (United States)

Lee, James J.; Jacobsen, Elizabeth A.; Ochkur, Sergei I; McGarry, Michael P.; Condjella, Rachel M.; Doyle, Alfred D.; Luo, Huijun; Zellner, Katie R.; Protheroe, Cheryl A.; Willetts, Lian; LeSuer, William E.; Colbert, Dana C.; Helmers, Richard A.; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A.

2012-01-01

The respective life histories of humans and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiological pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils and/or their effector functions. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide the experimental details, comparing and contrasting eosinophils and eosinophil effector functions in humans vs. mice. In particular, our review will provide a summation and an easy to use reference guide to important studies demonstrating that while differences exist, more often than not their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function, but instead, species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients. PMID:22935586

Mechanism for the differentiation of EoL-1 cells into eosinophils by histone deacetylase inhibitors.

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Kaneko, Motoko; Ishihara, Kenji; Takahashi, Aki; Hong, Jangja; Hirasawa, Noriyasu; Zee, Okpyo; Ohuchi, Kazuo

2007-01-01

EoL-1 cells have a FIP1L1-PDGFRA fusion gene which causes the transformation of eosinophilic precursor cells into leukemia cells. Recently, we suggested that the induction of differentiation of EoL-1 cells into eosinophils by the HDAC inhibitors apicidin and n-butyrate is due to the continuous inhibition of HDACs. However, neither apicidin nor n-butyrate inhibited the expression of FIP1L1-PDGFRA mRNA, although both these inhibitors suppressed cell proliferation. Therefore, in this study, we analyzed whether the levels of FIP1L1-PDGFRalpha protein and phosphorylated-Stat5 involved in the signaling for the proliferation of EoL-1 cells are attenuated by HDAC inhibitors. EoL-1 cells were incubated in the presence of apicidin, TSA or n-butyrate. FIP1L1-PDGFRalpha and phosphorylated-Stat5 were detected by Western blotting. Treatment of EoL-1 cells with apicidin at 100 nM or n-butyrate at 500 microM decreased the levels of FIP1L1-PDGFRalpha protein and phosphorylated-Stat5, while that with trichostatin A at 30 nM did not. The decrease in the level of FIP1L1-PDGFRalpha protein caused by apicidin and n-butyrate might be one of the mechanisms by which EoL-1 cells are induced to differentiate into eosinophils by these HDAC inhibitors.

Eosinophilic Esophagitis: MedlinePlus Health Topic

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... Esophagitis (EoE) (American Academy of Allergy, Asthma, and Immunology) Also in Spanish Latest News Eosinophilic Esophagitis May ... Pediatric and Adolescent Patients (American College of Gastroenterology) Topic Image Related Health Topics Eosinophilic Disorders Esophagus Disorders ...

Preparation and surface labeling of murine eosinophils

International Nuclear Information System (INIS)

Burgess, A.W.; Cruise, K.M.; Mitchell, G.F.; Watt, S.M.

1980-01-01

Eosinophilic polymorphonuclear leukocytes were isolated from the peritoneal cavity of BALB/c mice infected with the parasite Mesocestoides corti. Approximately 4 x 10 7 eosinophils (purity, 50%) could be harvested from each mouse. A high yield and purity of eosinophils was obtained from the peritoneal cells of infected male BALB/c mice using density centrifugation on a gradient of slightly hypotonic colloidal silica sol (Percoll). After initial irradiation of the mice to lower the lymphocyte contamination, subsequent density gradient (and where nescessary sedimentation velocity) centrifugation yielded 10 8 eosinophils (purity >95%) from six to eight mice. It was also possible to isolate small numbers of eosinophils (2 x 10 4 cells/minute, purity >99%) without irradiating the mice. This could be achieved by separating the density gradient purified peritoneal cells by light-scatter on a Becton-Dickinson cell sorter (FACS II). Analysis of proteins extracted from eosinophils using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed a group of high molecular weight proteins (between 250K and 160K) which were not as distinctive in the neutrophil profile. Surface labeling was performed, before the cell separation, by using 125 I and 1,3,4,6-tetrachloro-3α,6α-diphenylglycoluril. Only five 125 I-labeled proteins were detected initially (all with apparent molecular weights >50,000). No 125 I appeared to be associated with actin under the conditions used for surface labeling. Four of the eosinophil surface labeled proteins corresponded to surface labeled proteins on neutrophils, but the major surface component of the eosinophils (MW 79,000) appeared to be smaller than the major neutrophil protein (MW 90,000). (author)

Eosinophilic esophagitis

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... of the American Academy of Allergy, Asthma and Immunology. Dietary therapy and nutrition management of eosinophilic esophagitis: ... of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol Pract . 2017;5(2): ...

Atypical presentations of eosinophilic fasciitis

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Tulin Ergun

2016-01-01

Full Text Available Eosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia.

Eosinophilic fasciitis

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Karolina Niklas

2015-01-01

Full Text Available Eosinophilic fasciitis is a rare connective tissue disease with unclear etiology and pathogenesis. It is classified as a scleroderma-like syndrome. The disease is characterized by fibrosis of the skin and subcutaneous tissues with significant thickening of fascia. Visceral involvement is rare. Characteristic feature in laboratory tests is peripheral blood eosinophilia. Differential diagnosis should be performed, including ruling out systemic sclerosis, nephrogenic systemic fibrosis, eosinophilia-myalgia syndrome, scleromyxedema, hypereosinophilic syndrome or Churg-Strauss syndrome. Final diagnosis is confirmed by histopathological examination. In treatment of the disease corticosteroids and/or immunosuppressive drugs are used. Some other drugs showed activity in this disease e.g. dapsone, infiximab or rituximab. Prognosis is rather good but sometimes a long-term treatment is necessary. In this paper we summarized the current knowledge on eosinophilic fasciitis.

Inhibition of Asthma in OVA Sensitized Mice Model by a Traditional Uygur Herb Nepeta bracteata Benth.

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Jing Wang

2016-01-01

Full Text Available Asthma is a chronic lung inflammation which affects many people. As current therapies for asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. In this study, we investigated Nepeta bracteata Benth., a traditional Uygur Herb, for its therapeutics effect in OVA induced asthmatic mice model. Treatment of OVA sensitized asthma mice with extract from Nepeta bracteata Benth. demonstrated improved lung pathology, as well as reduced infiltration of eosinophil and neutrophil. Nepeta bracteata Benth. extract also contributed to the rebalance of Th17/Treg cell via decreasing the Th17 cell and increasing the Treg, which was corresponding with the inhibited Th17 cytokine response and increased IL-10 level. Moreover, the reduced TGF-β level and Smad2/3 protein level also suggested that Nepeta bracteata Benth. extract could inhibit TGF-β mediated airway remodelling as well. Taken together, these data suggested that Nepeta bracteata Benth. may be a novel candidate for future antiasthma drug development.

Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma

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Aguilar-Pimentel, Juan Antonio; Graessel, Anke; Alessandrini, Francesca

2017-01-01

)-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor) from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro. RESULTS: AIT...... combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA...... co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells. CONCLUSIONS: This proof of concept study shows that JAK inhibition did not inhibit...

Trisubstituted purine inhibitors of PDGFRα and their antileukemic activity in the human eosinophilic cell line EOL-1.

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Malínková, Veronika; Řezníčková, Eva; Jorda, Radek; Gucký, Tomáš; Kryštof, Vladimír

2017-12-15

Inhibition of protein kinases is a validated concept for pharmacological intervention in cancers. Many kinase inhibitors have been approved for clinical use, but their practical application is often limited. Here, we describe a collection of 23 novel 2,6,9-trisubstituted purine derivatives with nanomolar inhibitory activities against PDGFRα, a receptor tyrosine kinase often found constitutively activated in various tumours. The compounds demonstrated strong and selective cytotoxicity in the human eosinophilic leukemia cell line EOL-1, whereas several other cell lines were substantially less sensitive. The cytotoxicity in EOL-1, which is known to express the FIP1L1-PDGFRA fusion gene encoding an oncogenic kinase, correlated significantly with PDGFRα inhibition. EOL-1 cells treated with the compounds also exhibited dose-dependent inhibition of PDGFRα autophosphorylation and suppression of its downstream signaling pathways with concomitant G 1 phase arrest, confirming the proposed mechanism of action. Our results show that substituted purines can be used as platforms for preparing tyrosine kinase inhibitors with specific activity towards eosinophilic leukemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Eosinophilic Chronic Rhinosinusitis in Japan

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Junichi Ishitoya

Full Text Available ABSTRACT: Chronic rhinosinusitis is a heterogeneous disease. In Europe and the United States, it has recently been divided into two subgroups: chronic rhinosinusitis with nasal polyps (CRSwNP and chronic rhinosinusitis without nasal polyps (CRSsNP. The majority of CRSwNP cases have a strong tendency to recur after surgery and show eosinophil-dominant inflammation. However, this definition has proved difficult to apply in Japan and East Asia, because more than half of the CRSwNP cases do not exhibit eosinophil-dominant inflammation in these areas of the world. In Japan in the 1990s, refractory CRSwNP to the standard treatment was focused on in clinical studies and the term ''eosinophilic chronic rhinosinusitis'' (ECRS was introduced to identify this subgroup of chronic rhinosinusitis in 2001.ECRS is different from non-ECRS in terms of many clinical features: symptom appearance, occurrence site of nasal polyps, CT scan findings, the histology of nasal polyps, blood examination findings, clinical course after surgery, and co-morbid asthma, etc. In this review, we describe these clinical features and mention how to make a clinical diagnosis of ECRS as well as how to treat it. Finally, we discuss the pathophysiology of ECRS. The concept of ECRS in Japan would be applicable for CRSwNP in other countries including Europe and the United States. KEY WORDS: chronic rhinosinusitis, clinical feature, diagnosis, eosinophilic chronic rhinosinusitis, eosinophils

Characterization of a receptor for interleukin-5 on human eosinophils and the myeloid leukemia line HL-60

International Nuclear Information System (INIS)

Ingley, E.; Young, I.G.

1991-01-01

Interleukin-5 (IL-5) promotes the growth and differentiation of human eosinophils and may regulate the selective eosinophilia and eosinophil activation seen in certain diseases. Radiolabeled recombinant human IL-5 (hIL-5) was used to characterize the IL-5 receptor present on normal human eosinophils and on the myeloid leukemia line HL-60, which can be induced to differentiate into eosinophilic cells. Binding studies with eosinophils and HL-60 cells grown under alkaline conditions demonstrated similar high-affinity binding sites for hIL-5 on both cell types with kd values of approximately 400 pmol/L. The binding observed was specific in that it was not inhibited by hIL-3, human granulocyte-macrophage colony-stimulating factor, or hIL-2. Binding studies with a number of other human cell lines, including a B-lymphoma line, and with lymphocyte and neutrophil preparations were also performed, but IL-5 receptors were not detectable on these cells. The number of hIL-5 receptors on HL-60 cells could be correlated with its propensity to differentiate towards an eosinophilic cell type. Expression of hIL-5 receptors on HL-60 cells was upregulated by butyric acid under alkaline conditions, downregulated by hIL-3, virtually eliminated by dimethyl sulfoxide and hIL-5, while hIL-2 had no detectable effect. One major 125I-hIL-5-crosslinked complex of 75 to 85 Kd in Mr was detected on HL-60 cells using crosslinking agents giving a molecular mass of 55 to 60 Kd for the hIL-5 receptor itself. Studies using cellular autoradiography showed that IL-5 receptors were evenly distributed on eosinophils but that receptor distribution on HL-60 cells was noticeably heterogeneous. Eosinophils were the only cells in slides prepared from peripheral blood that had detectable levels of IL-5 receptors in agreement with the specific action of IL-5 on the human eosinophil lineage

Signal peptide of eosinophil cationic protein is toxic to cells lacking signal peptide peptidase

International Nuclear Information System (INIS)

Wu, C.-M.; Chang, Margaret Dah-Tsyr

2004-01-01

Eosinophil cationic protein (ECP) is a toxin secreted by activated human eosinophils. The properties of mature ECP have been well studied but those of the signal peptide of ECP (ECPsp) are not clear. In this study, several chimeric proteins containing N-terminal fusion of ECPsp were generated, and introduced into Escherichia coli, Pichia pastoris, and human epidermoid carcinoma cell line A431 to study the function of ECPsp. We found that expression of ECPsp chimeric proteins inhibited the growth of E. coli and P. pastoris but not A431 cells. Primary sequence analysis and in vitro transcription/translation of ECPsp have revealed that it is a potential substrate for human signal peptide peptidase (hSPP), an intramembrane protease located in endoplasmic reticulum. In addition, knockdown of the hSPP mRNA expression in ECPsp-eGFP/A431 cells caused the growth inhibitory effect, whereas complementally expression of hSPP in P. pastoris system rescued the cell growth. Taken together, we have demonstrated that ECPsp is a toxic signal peptide, and expression of hSPP protects the cells from growth inhibition

Elevated Plasma Chemokines for Eosinophils in Neuromyelitis Optica Spectrum Disorders during Remission

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Yanping Tong

2018-02-01

Full Text Available BackgroundA prominent pathological feature of neuromyelitis optica spectrum disorders (NMOSD is markedly greater eosinophilic infiltration than that seen in other demyelinating diseases, like multiple sclerosis (MS. Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (CCL11/eotaxin-1, CCL24/eotaxin-2, CCL26/eotaxin-3 and CCL13 [monocyte chemoattractant protein (MCP-4]. Moreover, CCL13 is part of the chemokine set that activates CCR2. The present study aimed to evaluate plasma levels of eotaxins (CCL11, CCL24, and CCL26 and MCPs (CCL13, CCL2, CCL8, and CCL7 in patients with NMOSD during remission.MethodsHealthy controls (HC; n = 30 and patients with MS (n = 47 and NMOSD (n = 58 in remission were consecutively enrolled in this study between January 2016 and August 2017. Plasma CCL11, CCL24, CCL26, CCL2, CCL8, CCL7, CCL13, tumor necrosis factor (TNF-α, and interleukin (IL-1β levels were detected using the human cytokine multiplex assay.ResultsPlasma CCL13, CCL11, and CCL26 levels were all significantly higher in patients with NMOSD than in HC and patients with MS. No significant differences were found in the CCL13, CCL11, or CCL26 levels between patients with NMOSD receiving and not receiving immunosuppressive therapy. The plasma levels of TNF-α and IL-1β, which stimulate the above chemokines, were higher in patients with NMOSD than in HC. There was no difference in CCL24 levels among the three groups. In most cases, the CCL7 levels were below the threshold value of the human cytokine multiplex assay, which is in line with other studies. Adjusted multiple regression analyses showed a positive association of CCL13 levels with the number of relapses after controlling gender, age, body mass index, and disease duration in patients with NMOSD.ConclusionThe study indicates that in NMOSD, the overproduction of cytokines such as IL-1β and TNF-α during remission stimulates eosinophilic chemoattractants such as

Eosinophilic pustular folliculitis: the transition in sex differences and interracial characteristics between 1965 and 2013.

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Nomura, Takashi; Katoh, Mayumi; Yamamoto, Yosuke; Kabashima, Kenji; Miyachi, Yoshiki

2015-04-01

Eosinophilic pustular folliculitis (EPF) is characterized by a non-infectious infiltration of eosinophils in the hair follicles. It has three variants: (i) classic EPF; (ii) immunosuppression-associated EPF, which herein is subdivided into HIV-associated (IS/HIV) and non-HIV-associated (IS/non-HIV); and (iii) infancy-associated EPF (I-EPF). The rarity of EPF has hindered our understanding of this entity. To examine the characteristics of EPF, with respect to age, sex, race, and chronology, published in case reports to date, we queried PubMed using the following terms: ("eosinophilic pustular folliculitis" [All Fields] OR "eosinophilic folliculitis" [All Fields]) AND ("1965/1/1" [PDAT]: "2013/12/31" [PDAT]). Additional Japanese cases were collected from Igaku Chuo Zasshi through Ichushi-Web, JDream III, and secondhand quotations from domestic periodicals published in Japan. Proceedings were excluded. The PubMed search produced 275 citations containing 358 cases of EPF (224 men, 132 women, and two of unspecified sex); these cases involved classic EPF (101 Japanese and 81 non-Japanese), IS/HIV (4 Japanese and 85 non-Japanese), IS/non-HIV (4 Japanese and 20 non-Japanese), and I-EPF (4 Japanese and 59 non-Japanese). Ichushi generated an additional 148 citations containing 207 cases of Japanese (148 men and 59 women), which included cases of classic EPF (181 cases), IS/HIV (14 cases), IS/non-HIV (9 cases), and I-EPF (3 cases). There was no sex difference in the classic EPF cases reported between 2003 and 2013, whereas IS/HIV, IS/non-HIV, and I-EPF were predominated by men. There is room for reconsideration of sex differences, particularly with regard to classic EPF. The rarity and specificity of I-EPF in Japan may reflect a state of uncertainty about this entity. © 2015 Japanese Dermatological Association.

Recombinant tumor necrosis factor alpha inhibits growth of methylcholanthrene-induced sarcoma and enhances natural killer activity of tumor-infiltrating lymphocytes in aging rats

International Nuclear Information System (INIS)

Ziolkowska, Maria; Nowak Joanna, J.; Janiak, Marek; Ryzewska, Alicja

1994-01-01

The effect of recombinant human tumor necrosis factors alpha (rHuTNF-α) on the growth of immunogenic, methylcholanthrene-induced sarcoma (MC-Sa) and natural killer (NK) cell activity of tumor-infiltrating lymphocytes (TIL) in adult and aging rats was investigated. In both groups of animals the growth of transplantable MC-Sa was markedly and similarly inhibited by multiple intratumoral (i.t.) injections of rHuTF-α. This effect was accompanied by stimulation of NK activity of tumor-infiltrating lymphocytes in adult as well as in aging rats. Studies ''in vitro'' demonstrated additionally that rHuTNF-α was a potent stimulator of NK but not of ADCC (antibody-dependent cellular cytotoxicity) activity of spleen lymphocytes from healthy animals. Our results indicate that the antitumor effect of TNF-α is comparable in adult and in aging rats bearing immunogenic MC-Sa. The inhibition of MC-Sa growth may be attributed not only to the TNF-α-induced necrosis of the neoplastic tissue but also to the ''in vivo'' stimulatory effect of this cytokine upon the NK-type function of lymphocytes infiltrating the tumor mass. (author). 31 refs, 5 figs, 2 tabs

Andrographolide Ameliorates Abdominal Aortic Aneurysm Progression by Inhibiting Inflammatory Cell Infiltration through Downregulation of Cytokine and Integrin Expression

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Ren, Jun; Liu, Zhenjie; Wang, Qiwei; Giles, Jasmine; Greenberg, Jason; Sheibani, Nader; Kent, K. Craig

2016-01-01

Abdominal aortic aneurysm (AAA), characterized by exuberant inflammation and tissue deterioration, is a common aortic disease associated with a high mortality rate. There is currently no established pharmacological therapy to treat this progressive disease. Andrographolide (Andro), a major bioactive component of the herbaceous plant Andrographis paniculata, has been found to exhibit potent anti-inflammatory properties by inhibiting nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity in several disease models. In this study, we investigated the ability of Andro to suppress inflammation associated with aneurysms, and whether it may be used to block the progression of AAA. Whereas diseased aortae continued to expand in the solvent-treated group, daily administration of Andro to mice with small aneurysms significantly attenuated aneurysm growth, as measured by the diminished expansion of aortic diameter (165.68 ± 15.85% vs. 90.62 ± 22.91%, P < 0.05). Immunohistochemistry analyses revealed that Andro decreased infiltration of monocytes/macrophages and T cells. Mechanistically, Andro inhibited arterial NF-κB activation and reduced the production of proinflammatory cytokines [CCL2, CXCL10, tumor necrosis factor α, and interferon-γ] in the treated aortae. Furthermore, Andro suppressed α4 integrin expression and attenuated the ability of monocytes/macrophages to adhere to activated endothelial cells. These results indicate that Andro suppresses progression of AAA, likely through inhibition of inflammatory cell infiltration via downregulation of NF-κB–mediated cytokine production and α4 integrin expression. Thus, Andro may offer a pharmacological therapy to slow disease progression in patients with small aneurysms. PMID:26483397

Esophageal microbiome in eosinophilic esophagitis.

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J Kirk Harris

Full Text Available The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis.In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD and normal mucosa using the Esophageal String Test (EST. Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease.Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects.Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD.

Human eosinophils constitutively express a unique serine protease, PRSS33.

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Toyama, Sumika; Okada, Naoko; Matsuda, Akio; Morita, Hideaki; Saito, Hirohisa; Fujisawa, Takao; Nakae, Susumu; Karasuyama, Hajime; Matsumoto, Kenji

2017-07-01

Eosinophils play important roles in asthma, especially airway remodeling, by producing various granule proteins, chemical mediators, cytokines, chemokines and proteases. However, protease production by eosinophils is not fully understood. In the present study, we investigated the production of eosinophil-specific proteases/proteinases by transcriptome analysis. Human eosinophils and other cells were purified from peripheral blood by density gradient sedimentation and negative/positive selections using immunomagnetic beads. Protease/proteinase expression in eosinophils and release into the supernatant were evaluated by microarray analysis, qPCR, ELISA, flow cytometry and immunofluorescence staining before and after stimulation with eosinophil-activating cytokines and secretagogues. mRNAs for extracellular matrix proteins in human normal fibroblasts were measured by qPCR after exposure to recombinant protease serine 33 (PRSS33) protein (rPRSS33), created with a baculovirus system. Human eosinophils expressed relatively high levels of mRNA for metalloproteinase 25 (MMP25), a disintegrin and metalloprotease 8 (ADAM8), ADAM10, ADAM19 and PRSS33. Expression of PRSS33 was the highest and eosinophil-specific. PRSS33 mRNA expression was not affected by eosinophil-activating cytokines. Immunofluorescence staining showed that PRSS33 was co-localized with an eosinophil granule protein. PRSS33 was not detected in the culture supernatant of eosinophils even after stimulation with secretagogues, but its cell surface expression was increased. rPRSS33 stimulation of human fibroblasts increased expression of collagen and fibronectin mRNAs, at least in part via protease-activated receptor-2 activation. Activated eosinophils may induce fibroblast extracellular matrix protein synthesis via cell surface expression of PRSS33, which would at least partly explain eosinophils' role(s) in airway remodeling. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier

Roles and Regulation of Gastrointestinal Eosinophils in Immunity and Disease

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Jung, YunJae; Rothenberg, Marc E.

2014-01-01

Eosinophils have been considered to be destructive end-stage effector cells that have a role in parasitic infections and allergy reactions by the release of their granule-derived cytotoxic proteins. However, an increasing number of experimental observations indicate that eosinophils also are multifunctional leukocytes involved in diverse inflammatory and physiologic immune responses. Under homeostatic conditions, eosinophils are particularly abundant in the lamina propria of the gastrointestinal tract where their involvement in various biological processes within the gastrointestinal tract has been posited. In this review, we summarize the molecular steps involved in eosinophil development and describe eosinophil trafficking to the gastrointestinal tract. We synthesize the current findings on the phenotypic and functional properties of gastrointestinal eosinophils and the accumulating evidence that they have a contributory role in gastrointestinal disorders, with a focus on primary eosinophilic gastrointestinal disorders. Finally, we discuss the potential role of eosinophils as modulators of the intestinal immune system. PMID:25049430

Eosinophils from Physiology to Disease: A Comprehensive Review

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Yacoub, Mona-Rita; Ripa, Marco; Mannina, Daniele; Cariddi, Adriana; Saporiti, Nicoletta; Ciceri, Fabio; Castagna, Antonella; Dagna, Lorenzo

2018-01-01

Despite being the second least represented granulocyte subpopulation in the circulating blood, eosinophils are receiving a growing interest from the scientific community, due to their complex pathophysiological role in a broad range of local and systemic inflammatory diseases as well as in cancer and thrombosis. Eosinophils are crucial for the control of parasitic infections, but increasing evidence suggests that they are also involved in vital defensive tasks against bacterial and viral pathogens including HIV. On the other side of the coin, eosinophil potential to provide a strong defensive response against invading microbes through the release of a large array of compounds can prove toxic to the host tissues and dysregulate haemostasis. Increasing knowledge of eosinophil biological behaviour is leading to major changes in established paradigms for the classification and diagnosis of several allergic and autoimmune diseases and has paved the way to a “golden age” of eosinophil-targeted agents. In this review, we provide a comprehensive update on the pathophysiological role of eosinophils in host defence, inflammation, and cancer and discuss potential clinical implications in light of recent therapeutic advances. PMID:29619379

Eosinophilic esophagitis-endoscopic distinguishing findings

OpenAIRE

Caetano, Ana Célia; Gonçalves, Raquel; Rolanda, Carla

2012-01-01

Eosinophilic esophagitis (EE) is the most frequent condition found in a group of gastrointestinal disorders called eosinophilic gastrointestinal diseases. The hypothetical pathophysiological mechanism is related to a hypersensitivity reaction. Gastroesophageal reflux disease- like complaints not ameliorated by acid blockade or occasional symptoms of dysphagia or food impaction are likely presentations of EE. Due to its unclear pathogenesis and unspecific symptoms, it is difficult to diagnose ...

Management guidelines of eosinophilic esophagitis in childhood

DEFF Research Database (Denmark)

Papadopoulou, A; Koletzko, S; Heuschkel, R

2014-01-01

OBJECTIVES: Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. With few exceptions, 15 eosinophils per high-power field...... was obtained during 3 face-to-face meetings of the Gastroenterology Committee and 1 teleconference. RESULTS: The cornerstone of treatment is an elimination diet (targeted or empiric elimination diet, amino acid-based formula) and/or swallowed, topical corticosteroids. Systemic corticosteroids are reserved...

IL-3 maintains activation of the P90S6K/RPS6 pathway and increases translation in human eosinophils1

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Esnault, Stephane; Kelly, Elizabeth A.B.; Shen, Zhong-Jian; Johansson, Mats W.; Malter, James S.; Jarjour, Nizar N.

2015-01-01

IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines IL-5, IL-3, and GM-CSF are typically present in atopic diseases including allergic asthma. Due to the functional redundancy of these 3 cytokines on eosinophils and the loss of IL-5 receptor on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these 3 cytokines signal through a common β-chain receptor, and yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce production of proteins such as semaphorin-7A without affecting mRNA level suggests a unique influence by IL-3 on translation. The purpose of this study is to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared to IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein (RP) S6 and the upstream kinase, p90S6K. Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared to circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations place IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. PMID:26276876

Eosinophilic esophagitis: clinical manifestations, diagnosis, and treatment Esofagitis eosinofílica: clínica, diagnóstico y tratamiento

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A. J. Lucendo Villarín

2009-01-01

Full Text Available Eosinophilic esophagitis (EE is a chronic inflammatory, immunoallergic disease of the esophagus that represents the most common eosinophilic gut disease. Understanding and diagnosis regarding this condition have greatly increased in recent years, particularly in Europe and North America, in parallel with other allergic disorders. It consists of dense esophageal infiltration with eosinophils in the absence of gastro-esophageal reflux (GER. It involves individuals at all ages, and is particularly common in males during childhood and up to the 5th decade of life. It manifests with chronic, intermittent esophageal symptoms that predominantly include dysphagia, food impaction episodes, and GER-attributable complaints that do not respond to antisecretory therapy. Endoscopically, EE is a polymorphous disease that presents with various changes in esophageal caliber, and subtle changes in mucosal appearance, which lead to biopsy collection as a key procedure for diagnosis. Management must be multidisciplinary, including gastroenterologists, pathologists, allergologists, and also nutrition specialists in pediatric cases. Regarding therapy, dietary food restrictions are especially useful in the management of pediatric EE, but effectiveness is lower in the adult, maybe because of a greater involvement of air allergens. Drug use is standard, particularly involving topical steroids, which may revert manifestations and histological lesions, even though recurrence following discontinuation is common.

Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils

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Jing Zhu

2018-06-01

Full Text Available IL-1 family regulatory cytokine IL-37b can suppress innate immunity and inflammatory activity in inflammatory diseases. In this study, IL-37b showed remarkable in vitro suppression of inflammatory tumor necrosis factor-α, IL-1β, IL-6, CCL2, and CXCL8 production in the coculture of human primary eosinophils and human bronchial epithelial BEAS-2B cells with the stimulation of bacterial toll-like receptor-2 ligand peptidoglycan, while antagonizing the activation of intracellular nuclear factor-κB, PI3K–Akt, extracellular signal-regulated kinase 1/2, and suppressing the gene transcription of allergic inflammation-related PYCARD, S100A9, and CAMP as demonstrated by flow cytometry, RNA-sequencing, and bioinformatics. Results therefore elucidated the novel anti-inflammation-related molecular mechanisms mediated by IL-37b. Using the house dust mite (HDM-induced humanized asthmatic NOD/SCID mice for preclinical study, intravenous administration of IL-37b restored the normal plasma levels of eosinophil activators CCL11 and IL-5, suppressed the elevated concentrations of Th2 and asthma-related cytokines IL-4, IL-6, and IL-13 and inflammatory IL-17, CCL5, and CCL11 in lung homogenate of asthmatic mice. Histopathological results of lung tissue illustrated that IL-37b could mitigate the enhanced mucus, eosinophil infiltration, thickened airway wall, and goblet cells. Together with similar findings using the ovalbumin- and HDM-induced allergic asthmatic mice further validated the therapeutic potential of IL-37b in allergic asthma. The above results illustrate the novel IL-37-mediated regulation of intracellular inflammation mechanism linking bacterial infection and the activation of human eosinophils and confirm the in vivo anti-inflammatory activity of IL-37b on human allergic asthma.

Leukotactin-1/CCL15 induces cell migration and differentiation of human eosinophilic leukemia EoL-1 cells through PKCdelta activation.

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Lee, Ji-Sook; Kim, In Sik

2010-06-01

Leukotactin-1 (Lkn-1)/CCL15 is a CC chemokine that binds to the CCR1 and CCR3. Lkn-1 functions as an essential factor in the migration of monocytes, lymphocytes, and neutrophils. Although eosinophils express both receptors, the role of Lkn-1 in immature eosinophils remains to be elucidated. In this present study, we investigated the contribution of the CCR1-binding chemokines to chemotactic activity and in the differentiation in the human eosinophilic leukemia cell line EoL-1. Lkn-1 induced the stronger migration of EoL-1 cells than other CCR1-binding chemokines such as RANTES/CCL5, MIP-1alpha/CCL3 and HCC-4/CCL16. Lkn-1-induced chemotaxis was inhibited by pertussis toxin, an inhibitor of G(i)/G(o) protein; U73122, an inhibitor of phospholipase C and rottlerin, an inhibitor of protein kinase C delta (PKCdelta). Lkn-1 increased PKCdelta activity, which was partially blocked by the pertussis toxin and U73122. Lkn-1 enhanced the butyric acid-induced differentiation via PKCdelta after binding to the increased CCR1 because Lkn-1 caused EoL-1 cells to change morphologically into mature eosinophil-like cells. Likewise, Lkn-1 increased the expression of both eosinophil peroxidase (EPO) and the major basic protein (MBP). PKCdelta activation due to Lkn-1 is involved in migration, as well as the butyric acid-induced differentiation. This finding contributes to an understanding of CC chemokines in eosinophil biology and to the development of novel therapies for the treatment of eosinophilic disorders. This study suggests the pivotal roles of Lkn-1 in the regulation of the movement and development of eosinophils.

Regulation of Spontaneous Eosinophil Apoptosis—A Neglected Area of Importance

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Pinja Ilmarinen

2014-01-01

Full Text Available Asthma is characterized by the accumulation of eosinophils in the airways in most phenotypes. Eosinophils are inflammatory cells that require an external survival-prolonging stimulus such as granulocyte macrophage-colony-stimulating factor (GM-CSF, interleukin (IL-5, or IL-3 for survival. In their absence, eosinophils are programmed to die by spontaneous apoptosis in a few days. Eosinophil apoptosis can be accelerated by Fas ligation or by pharmacological agents such as glucocorticoids. Evidence exists for the relevance of these survival-prolonging and pro-apoptotic agents in the regulation of eosinophilic inflammation in inflamed airways. Much less is known about the physiological significance and mechanisms of spontaneous eosinophil apoptosis even though it forms the basis of regulation of eosinophil longevity by pathophysiological factors and pharmacological agents. This review concentrates on discussing the mechanisms of spontaneous eosinophil apoptosis compared to those of glucocorticoid- and Fas-induced apoptosis. We aim to answer the question whether the external apoptotic stimuli only augment the ongoing pathway of spontaneous apoptosis or truly activate a specific pathway.

Solitary eosinophilic granuloma of humerus in a 2-month-old infant: A case report with 3 years follow-up

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Prateek S Joshi

2015-01-01

Full Text Available Eosinophilic granulomais (EG a benign self-limiting disease which belongs to the spectrum of Langerhans cell histiocytosis. It is characterized by single or multiple skeletal lesions involving skull, mandible, ribs, spine and long bones predominately in children <12 years. We report a relatively rare case of left proximal humerus solitary EG in a month old infant who was brought to us with reduced movements of left upper limb and swelling of left shoulder. X-ray revealed osteolytic lesion in left upper humerus. No associated lesions were revealed by other imaging modalities. Open biopsy and curettage of lesion revealed proliferation of histiocytes with an infiltration of eosinophils. Immunohistochemistry was positive for S-100 and CD1a. Hence, diagnosis of solitary EG was made. Baby was followed up every 6 monthly for 3 years. There was no evidence of recurrence or detection of new lesion elsewhere at last follow-up.

Eosinophilic cystitis

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Mosholt, Karina Sif Søndergaard; Dahl, Claus; Azawi, Nessn Htum

2014-01-01

Eosinophilic cystitis (EC) is a rare disease. We describe three cases, where presentations of the disease are similar. To highlight probable causes of the disease, symptoms, clinical findings and treatment modalities, we reviewed 56 cases over a 10-year period. The most common symptoms were...

Esophagitis dissecans associated with eosinophilic esophagitis in an adolescent

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Marjorie-Anne R. Guerra

2015-03-01

Full Text Available Esophagitis dissecans superficialis and eosinophilic esophagitis are distinct esophageal pathologies with characteristic clinical and histologic findings. Esophagitis dissecans superficialis is a rare finding on endoscopy consisting of the peeling of large fragments of esophageal mucosa. Histology shows sloughing of the epithelium and parakeratosis. Eosinophilic esophagitis is an allergic disease of the esophagus characterized by eosinophilic inflammation of the epithelium and symptoms of esophageal dysfunction. Both of these esophageal processes have been associated with other diseases, but there is no known association between them. We describe a case of esophagitis dissecans superficialis and eosinophilic esophagitis in an adolescent patient. To our knowledge, this is the first case describing an association between esophageal dissecans superficialis and eosinophilic esophagitis.

The potential implication of eosinophil activation in the pathogenesis ...

African Journals Online (AJOL)

Ehab

The potential implication of eosinophil activation in the pathogenesis of childhood asthma. INTRODUCTION. Asthma is recognized as an eosinophil mediated inflammation of the airways1. Eosinophils are major contributors to the damage in the airways of asthmatic patients which when activated, degranulate and release ...

dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses.

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Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

2017-08-04

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.

IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils.

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Esnault, Stephane; Kelly, Elizabeth A B; Shen, Zhong-Jian; Johansson, Mats W; Malter, James S; Jarjour, Nizar N

2015-09-15

IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a result of the functional redundancy of these three cytokines on eosinophils and the loss of IL-5R on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these three cytokines signal through a common β-chain receptor but yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce the production of proteins, such as semaphorin-7A, without affecting mRNA levels suggests a unique influence of IL-3 on translation. The purpose of this study was to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared with IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF, or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein S6 (RPS6) and the upstream kinase 90-kDa ribosomal S6 kinase (p90S6K). Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared with circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations identify IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. Copyright © 2015 by The American Association of Immunologists, Inc.

Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis

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Sato, Hiroki; Nakajima, Nao; Takahashi, Kazuya; Hasegawa, Go; Mizuno, Ken-ichi; Hashimoto, Satoru; Ikarashi, Satoshi; Hayashi, Kazunao; Honda, Yutaka; Yokoyama, Junji; Sato, Yuichi; Terai, Shuji

2017-01-01

AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder (EoGD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis (EoE), subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal myositis (EoEM), identified by endoscopy, manometry and serum immunoglobulin E levels (s-IgE), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples. RESULTS In five patients with EoE, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with sEoE and four with EoEM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with EoE and sEoE with some variation, while EoEM was associated with hypercontractile or hypertensive peristalsis, with elevated s-IgE. Histology revealed the following eosinophils per high-power field values. EoE = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; sEoE = 3 in the epithelium and 35 in the subepithelium (conventional biopsy); EoEM = none in the epithelium, 10.7 ± 11.7 in the subepithelium (conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria (peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to EoE. Eotaxin-3, IL-5 and IL-13 were overexpressed in EoE. CONCLUSION Based on clinical and histological data, we identified criteria, which differentiated between EoE, sEoE and EoEM, and reflected a different pathogenesis between these esophageal EoGDs. PMID:28428721

Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis.

Science.gov (United States)

Sato, Hiroki; Nakajima, Nao; Takahashi, Kazuya; Hasegawa, Go; Mizuno, Ken-Ichi; Hashimoto, Satoru; Ikarashi, Satoshi; Hayashi, Kazunao; Honda, Yutaka; Yokoyama, Junji; Sato, Yuichi; Terai, Shuji

2017-04-07

To define clinical criteria to differentiate eosinophilic gastrointestinal disorder (EoGD) in the esophagus. Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis (EoE), subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal myositis (EoEM), identified by endoscopy, manometry and serum immunoglobulin E levels (s-IgE), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples. In five patients with EoE, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with sEoE and four with EoEM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with EoE and sEoE with some variation, while EoEM was associated with hypercontractile or hypertensive peristalsis, with elevated s-IgE. Histology revealed the following eosinophils per high-power field values. EoE = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; sEoE = 3 in the epithelium and 35 in the subepithelium (conventional biopsy); EoEM = none in the epithelium, 10.7 ± 11.7 in the subepithelium (conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria (peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to EoE. Eotaxin-3, IL-5 and IL-13 were overexpressed in EoE. Based on clinical and histological data, we identified criteria, which differentiated between EoE, sEoE and EoEM, and reflected a different pathogenesis between these esophageal EoGDs.

2013 Update on Celiac Disease and Eosinophilic Esophagitis

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Marco Astegiano

2013-08-01

Full Text Available Celiac disease is a chronic, immune-mediated disorder, characterized by small intestinal inflammation and villous atrophy after the ingestion of gluten by genetically susceptible individuals. Several extraintestinal manifestations have been associated to celiac disease. Eosinophilic esophagitis is a primary disorder of the esophagus characterized by upper gastrointestinal symptoms, absence of gastroesophageal reflux disease and more than 15 eosinophils per high-power field in biopsy specimens. Both celiac disease and eosinophilic esophagitis are caused by aberrant, but distinct, immune responses to ingested antigens and can be responsive to restricted food intake. The aim of this review is to assess whether there is an association between these two pathologies. In the majority of the studies examined, including the studies in pediatric population, the prevalence of eosinophilic esophagitis in subjects with celiac disease was about 10-times that of the general population. We suggest searching for eosinophilic esophagitis in all children undergoing endoscopy for suspicious celiac disease.

Ethanol Extract of Sanguisorbae Radix Inhibits Mast Cell Degranulation and Suppresses 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions

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Ju-Hye Yang

2016-01-01

Full Text Available Sanguisorbae Radix (SR is well known as herbal medicine named “Zi-Yu” in Korea, which is the dried roots of Sanguisorba officinalis L. (Rosacease. We investigated the underlying mechanism on the inhibition of atopic dermatitis (AD of an ethanol extract of SR (ESR using 2,4-dinitrochlorobenzene- (DNCB- induced AD mice model. Oral administration of ESR significantly suppressed DNCB-induced AD-like symptoms such as scratching behavior, ear thickness, epidermal thickness, and IgE levels. To investigate the effects of ESR treatment on degranulation of IgE/Ag-activated mouse bone marrow-derived mast cells (BMMCs, we measured the release of β-hexosaminidase (β-HEX, degranulation marker. ESR decreased the infiltration of eosinophils and mast cells into the AD skin lesions. Furthermore, ESR significantly inhibited degranulation of IgE/Ag-activated BMMCs. We have demonstrated that ESR decreased AD symptoms in mice and inhibits degranulation of IgE/Ag-activated mast cells. Our study suggests that ESR may serve as a potential therapeutic candidate for the treatment of AD symptoms.

Genetics Home Reference: PDGFRA-associated chronic eosinophilic leukemia

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... link) Genetic Testing Registry: Idiopathic hypereosinophilic syndrome Other Diagnosis and Management Resources (3 links) Cancer.Net: Leukemia - Eosinophilic: Treatment MedlinePlus Encyclopedia: Eosinophil Count - Absolute Seattle ...

Emerging Roles for Eosinophils in the Tumor Microenvironment.

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Reichman, Hadar; Karo-Atar, Danielle; Munitz, Ariel

2016-11-01

Eosinophils are evolutionary conserved cells largely studied in the context of allergy. Although eosinophils were first described in tumors more than 120 years ago, their roles in cancer are often overlooked. This is puzzling given their potent immune modulatory, cytotoxic, and/or tissue repair capabilities, and recent studies demonstrating key roles for eosinophils in contexts far beyond their 'classical' field (e.g., metabolism, thermogenesis, and tissue regeneration). Recent data suggest that this frequently ignored cell is emerging as a potent immune effector and immune modulator in the tumor microenvironment. This review discusses the relevance of eosinophils to tumorigenesis and the potential to harness their function in cancer therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevalence of eosinophilic esophagitis in patients with gastroesophageal reflux symptoms: A cross-sectional study from a tertiary care hospital in North India.

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Baruah, Bhaskarjyoti; Kumar, Tarun; Das, Prasenjit; Thakur, Bhaskar; Sreenivas, Vishnubatla; Ahuja, Vineet; Gupta, Siddhartha Datta; Makharia, Govind K

2017-09-01

Eosinophilic esophagitis (EoE) is being recognized increasingly all over the globe; Indian data is however sparse. We screened patients with symptoms of gastroesophageal reflux disease (GERD) for presence of EoE in them. Consecutive patients with symptoms suggestive of GERD underwent gastroduodenoscopy and esophageal biopsies, obtained from both the upper esophagus (5 cm below the upper esophageal sphincter) and lower esophagus (5 cm above gastroesophageal junction), as well as from any other endoscopically visible abnormal mucosa. Demographic and clinical characteristics, endoscopic findings, peripheral blood eosinophilic count, and history of use of proton-pump inhibitors (PPIs) were analyzed. Stool examination was done to rule out parasitoids. EoE was diagnosed if number of mucosal eosinophil infiltrate was >20 per high-power field. In the latter, Warthin-Starry stain was performed to rule out presence of H elicobacter pylori. Of 190 consecutive patients with symptoms of GERD screened, esophageal biopsies were available in 185 cases. Of them, 6 had EoE, suggesting a prevalence of 3.2% among patients with GERD. On univariate analysis, history of allergy, non-response to PPI, and absolute eosinophil counts and on multivariable analysis, history of allergy and no response to PPIs were significant predictors of EoE. Presence of EOE did not correlate with severity of reflux symptoms. In this hospital-based study from northern part of India, prevalence of EoE in patients with GERD was 3.2%. EoE should be considered as a diagnostic possibility, especially in those with history of allergy, no-response to PPI, and absolute eosinophil count of ≥250/cumm.

New Insights into Eosinophilic Otitis Media.

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Kanazawa, Hiromi; Yoshida, Naohiro; Iino, Yukiko

2015-12-01

Eosinophilic otitis media (EOM) is a type of intractable otitis media that occurs mainly in patients with bronchial asthma (BA). In 2011, the diagnostic criteria for EOM were established. EOM is characterized by the presence of a highly viscous yellowish effusion containing eosinophils and immunoglobulin E (IgE), eosinophil chemoattractants, such as eosinophil cationic protein, interleukin-5, and eotaxin. Local sensitization against foreign agents such as fungi or bacteria (e.g., Staphylococcus aureus) may result in local IgE production in the middle ear and may be responsible for the severity of EOM. The clinical features of EOM closely resemble localized eosinophilic granulomatosis polyangiitis, therefore it is necessary to be vigilant to the symptoms of mononeuritis, polyneuritis, and skin purpura during diagnosis. Standard treatment for EOM is the instillation of triamcinolone acetonide into the mesotympanum. However, severe cases exhibiting strong inflammation and otorrhea are not easily controlled with antibiotics and/or corticosteroids. We proposed the introduction of a severity score to evaluate the severity of EOM. This score correlated with local IgE levels in middle ear effusion. Clinically, the risk factors associated with this severity score were body mass index, and the duration of bronchial asthma (from the onset of BA to the age of the first consultation of otitis media to our hospital). We emphasize that early diagnosis and adequate treatment are vital in preventing progressive and sudden hearing loss resulting from EOM.

Eosinophilic Dermatosis of Hematologic Malignancy.

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Lucas-Truyols, S; Rodrigo-Nicolás, B; Lloret-Ruiz, C; Quecedo-Estébanez, E

Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Cytological diagnostic of lymphadenitis tuberculosis by eosinophilic material

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Delyuzar; Amir, Z.; Kusumawati, L.

2018-03-01

AFB sputum and chest X-ray are used to identify patients with pulmonary TB. For extrapulmonary TB, fine needle aspiration cytology is needed, even though occasionally found not atypical feature in the form of eosinophilic material with dark brown particles, suspected as TB. This research was to show that eosinophilic material with dark brown particles is accurate as new criteria for the cytological diagnosis of TB. By performing fine needle aspiration biopsy stained with Giemsa, if an eosinophilic material with dark brown particles was encountered, we continued with Ziehl-Neelsen AFB stain and confirmed with PCR. To assess accuracy, we used a diagnostic test to evaluate sensitivity and specificity of eosinophilic material with dark brown particles by using AFB and PCR as the gold standard. The sensitivity and specificity of cytological diagnosis in tuberculosis of eosinophilic material with dark brown particles were 93.65% and 70.99%, respectively if confirmed with AFB. On the other hand, if confirmed with PCR using Mycobacterium tuberculosis DNA, the sensitivity and specificity were 98.95% and 96.79%, respectively. In conclusion, eosinophilic masses with dark brown particles is accurate as new criteria of TB diagnostic cytology with high sensitivity and specificity confirmed with AFB and PCR test.

Eosinophils are rare in biopsy specimens of psoriasis vulgaris.

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Rosa, Gabriela; Fernandez, Anthony P; Schneider, Sarah; Billings, Steven D

2017-12-01

Histological features of lesional biopsies can be helpful in distinguishing psoriasis subtypes from disease mimickers. However, occasionally, classic histological features are not sufficient for distinction, and additional clues would be useful. There is a common belief that the presence of eosinophils in skin biopsies argues against psoriasis, but actual literature is scant. Skin biopsies with a diagnosis of psoriasis from 2013 to 2016 were reviewed. For inclusion, both histological and clinical features were required to be consistent with psoriasis. For biopsies meeting inclusion criteria, a detailed evaluation for typical histological parameters of psoriasis, as well as presence of dermal eosinophils, was performed. Of 85 cases meeting inclusion criteria, all had either individual or grouped intracorneal neutrophils and dilated papillary blood vessels. Diminished or complete loss of the granular cell layer was seen in 83 cases (98%), and parakeratosis was seen in 84 cases (99%). Alternatively, dermal eosinophils were seen in only 15 cases (18%). Of cases with eosinophils, none had more than 3 eosinophils upon examination of the entire dermis. Active treatment did not appear to impact presence/absence or numbers of eosinophils. Eosinophils are uncommon in psoriasis biopsies, and when present, they are found in small numbers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Goishi tea consumption inhibits airway hyperresponsiveness in BALB/c mice

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Nakamura Hiroyuki

2011-08-01

Full Text Available Abstract Background Airway hyperresponsiveness (AHR is one of the important traits that characterize bronchial asthma. Goishi tea is a post-heating fermented tea that has been reported to have higher free radical scavenging activity. In this study, we evaluated the prophylactic effects of Goishi tea on AHR in BALB/c mice. Results The number of inflammatory cells in BAL fluid was considerably reduced in Goishi tea/Der f and Gallic acid/Der f groups as compared with Tap water/Der f group. Regarding inflammatory cells in BAL, a significant reduction of eosinophils and neutrophils was observed in Goishi tea-treated mice (p Der f group (p Der f group. In asthmatic mice (Tap water/Der f group, the intensity of airway resistance increased simultaneously with the increase in acetylcholine concentration in a dose-dependant way. AHR was significantly inhibited in Goishi tea/Der f and Gallic acid/Der f (p Der f group. Regarding serum specific-IgG1, significantly lower levels of this antibody were observed in Goishi tea/Der f and Gallic acid/Der f groups as compared with the Tap water/Der f group (p Conclusions The results suggest that Goishi tea consumption exerted an inhibitory effect on eosinophilic and neutrophilic infiltration in the lung, attenuated the increase in airway resistance and increased the production of adiponectin; thus reducing Der f induced allergic inflammatory process in mice.

Eosinophils in Homeostasis and Their Contrasting Roles during Inflammation and Helminth Infections.

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Strandmark, Julia; Rausch, Sebastian; Hartmann, Susanne

2016-01-01

Eosinophil numbers are highly elevated during helminth infections and a range of allergic and inflammatory disorders, but eosinophils are also present in several tissues in the absence of infection. Indeed, new findings demonstrate that eosinophils may be involved in events as diverse as glucose metabolism, mammary gland development, intestinal health, tissue remodeling, thymic selection, and B-cell survival. Although eosinophils often correlate with pathological parameters during conditions such as inflammatory bowel disease and asthma, the evidence for their contribution to tissue pathology remains controversial. Recent research suggests that eosinophils may have additional roles in these settings that are related to control and resolution of inflammation. Controversy also surrounds the involvement of eosinophils in anti-helminth immunity. Their assumed role in fighting parasites has increasingly been questioned, particularly as a result of data from studies of eosinophil-ablated mouse strains in which either no or only very moderate effects on helminth survival has been reported. Helminths are masters of immune regulation, but whether they actively suppress eosinophil function has rarely been considered. Thus, the purpose of this review is threefold: (1) to summarize our knowledge of the wide range of functions of eosinophils during homeostasis, (2) to discuss the role of eosinophil during inflammation and the recent discovery of eosinophils as mediators of inflammatory resolution, and (3) to summarize data on the effect of eosinophils on helminth infections and discuss the possibility of helminth-mediated modulation of eosinophils.

Exosome secretion by eosinophils: A possible role in asthma pathogenesis.

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Mazzeo, Carla; Cañas, José Antonio; Zafra, Maria Paz; Rojas Marco, Ainara; Fernández-Nieto, Mar; Sanz, Veronica; Mittelbrunn, María; Izquierdo, Manuel; Baixaulli, Francesc; Sastre, Joaquín; Del Pozo, Victoria

2015-06-01

Eosinophils secrete several granules that are involved in the propagation of inflammatory responses in patients with pathologies such as asthma. We hypothesized that some of these granules are exosomes, which, when transferred to the recipient cells, could modulate asthma progression. Eosinophils were purified from peripheral blood and cultured with or without IFN-γ or eotaxin. Multivesicular bodies (MVBs) in eosinophils were studied by using fluorescence microscopy, transmission electron microscopy (TEM), and flow cytometry. Exosome secretion was measured and exosome characterization was performed with TEM, Western blotting, and NanoSight analysis. Generation of MVBs in eosinophils was confirmed by using fluorescence microscopy and flow cytometry and corroborated by means of TEM. Having established that eosinophils contain MVBs, our aim was to demonstrate that eosinophils secrete exosomes. To do this, we purified exosomes from culture medium of eosinophils and characterized them. Using Western blot analysis, we demonstrated that eosinophils secreted exosomes and that the discharge of exosomes to extracellular media increases after IFN-γ stimulation. We measured exosome size and quantified exosome production from healthy and asthmatic subjects using nanotracking analysis. We found that exosome production was augmented in asthmatic patients. Our findings are the first to demonstrate that eosinophils contain functional MVBs and secrete exosomes and that their secretion is increased in asthmatic patients. Thus exosomes might play an important role in the progression of asthma and eventually be considered a biomarker. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

CXCR3 expression and activation of eosinophils

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Jinquan, T; Jing, C; Jacobi, H H

2000-01-01

CXC chemokine receptor 3 (CXCR3), predominately expressed on memory/activated T lymphocytes, is a receptor for both IFN-gamma-inducible protein-10 (gamma IP-10) and monokine induced by IFN-gamma (Mig). We report a novel finding that CXCR3 is also expressed on eosinophils. gamma IP-10 and Mig induce...... in eosinophils are up- and down-regulated by IL-2 and IL-10, respectively, as detected using flow cytometry, immunocytochemical assay, and a real-time quantitative RT-PCR technique. gamma IP-10 and Mig act eosinophils to induce chemotaxis via the cAMP-dependent protein kinase A signaling pathways. The fact...

Nutritional management of Eosinophilic Gastroenteropathies: Case series from the community

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Basilious Alfred

2011-05-01

Full Text Available Abstract Eosinophilic gastroenteropathies, such as eosinophilic esophagitis and eosinophilic colitis, have classically been treated with swallowed inhaled corticosteroids or oral corticosteroids. More recent studies have found elimination and elemental diets to be effective treatment alternatives to steroids. In this case series we describe the treatment of three children using nutritional management in a community setting. Elimination diets and elemental diets based on patch testing and skin prick tests reduced the eosinophil counts to normal levels in all three children. Food items which tested positive were then reintroduced while symptoms and eosinophil counts were monitored. Nutritional management of eosinophilic esophagitis and eosinophilic colitis was found to be effective in reducing symptoms. However, obstacles facing patients who choose this type of therapy include limitations due to the cost of repeated endoscopies, palatability of elimination/elemental diets and the availability of subspecialists trained in management (e.g. Allergy, Gastroenterology, and Pathology. It may be a worthwhile endeavour to overcome these obstacles as nutritional management minimizes the potential long-term effects of chronic steroid therapy.

The expanding role(s) of eosinophils in health and disease

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Jacobsen, Elizabeth A.; Helmers, Richard A.

2012-01-01

Surprisingly, the role(s) of eosinophils in health and disease is often summarized by clinicians and basic research scientists as a pervasive consensus opinion first learned in medical/graduate school. Eosinophils are rare white blood cells whose activities are primarily destructive and are only relevant in parasitic infections and asthma. However, is this consensus correct? This review argues that the wealth of available studies investigating the role(s) of eosinophils in both health and disease demonstrates that the activities of these granulocytes are far more expansive and complex than previously appreciated. In turn, this greater understanding has led to the realization that eosinophils have significant contributory roles in a wide range of diseases. Furthermore, published studies even implicate eosinophil-mediated activities in otherwise healthy persons. We suggest that the collective reports in the literature showing a role for eosinophils in an ever-increasing number of novel settings highlight the true complexity and importance of this granulocyte. Indeed, discussions of eosinophils are no longer simple and more often than not now begin with the question/statement “Did you know …?” PMID:22936660

Asthma Control and Sputum Eosinophils: A Longitudinal Study in Daily Practice.

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Demarche, Sophie F; Schleich, Florence N; Paulus, Virginie A; Henket, Monique A; Van Hees, Thierry J; Louis, Renaud E

Longitudinal trials have suggested that asthma control may be influenced by fluctuations in eosinophilic inflammation. This association has however never been confirmed in daily practice. To investigate the relationship between asthma control and sputum eosinophils in clinical practice. A retrospective longitudinal study was conducted on 187 patients with asthma with at least 2 successful sputum inductions at our Asthma Clinic. Linear mixed models were used to assess the relationship between asthma control and individual changes in sputum eosinophils. Receiver-operating characteristic curves were constructed to define minimal important differences (MIDs) of sputum eosinophils associated with a change of at least 0.5 in Asthma Control Questionnaire (ACQ) score. Then, a validation cohort of 79 patients with asthma was recruited to reassess this relationship and the accuracy of the MID values. A multivariate analysis showed that asthma control was independently associated with individual fluctuations in sputum eosinophil count (P eosinophilic asthma, we calculated a minimal important decrease of 4.3% in the percentage of sputum eosinophils (area under the curve [AUC], 0.69; P eosinophils and the accuracy of the MIDs of sputum eosinophils were confirmed in the validation cohort. At the individual level, asthma control was associated with fluctuations in sputum eosinophil count over time. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Extracellular microvesicle production by human eosinophils activated by “inflammatory” stimuli

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Praveen Akuthota

2016-10-01

Full Text Available A key function of human eosinophils is to secrete cytokines, chemokines and cationic proteins, trafficking and releasing these mediators for roles in inflammation and other immune responses. Eosinophil activation leads to secretion of pre-synthesized granule-stored mediators through different mechanisms, but the ability of eosinophils to secrete extracellular vesicles (EVs, very small vesicles with preserved membrane topology, is still poorly understood. In the present work, we sought to identify and characterize EVs released from human eosinophils during different conditions: after a culturing period or after isolation and stimulation with inflammatory stimuli, which are known to induce eosinophil activation and secretion: CCL11 (eotaxin-1 and tumor necrosis factor alpha (TNF-α. EV production was investigated by nanoscale flow cytometry, conventional transmission electron microscopy (TEM and pre-embedding immunonanogold EM. The tetraspanins CD63 and CD9 were used as EV biomarkers for both flow cytometry and ultrastructural immunolabeling. Nanoscale flow cytometry showed that human eosinophils produce EVs in culture and that a population of EVs expressed detectable CD9, while CD63 was not consistently detected. When eosinophils were stimulated immediately after isolation and analyzed by TEM, EVs were clearly identified as microvesicles (MVsoutwardly budding off the plasma membrane. Both CCL11 and TNF-α induced significant increases of MVs compared to unstimulated cells.TNF-α induced amplified release of MVs more than CCL11. Eosinophil MV diameters varied from 20-1000 nm. Immunonanogold EM revealed clear immunolabeling for CD63 and CD9 on eosinophil MVs, although not all MVs were labeled. Altogether, we identified, for the first time, that human eosinophils secrete MVs and that this production increases in response to inflammatory stimuli. This is important to understand the complex secretory activities of eosinophils underlying immune

Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease

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Tashkin DP

2018-01-01

Full Text Available Donald P Tashkin,1 Michael E Wechsler2 1Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2Department of Medicine, National Jewish Health, Denver, CO, USA Abstract: COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. Keywords: lung disease, pulmonary diseases, corticosteroids, asthma, pneumonia

Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis.

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Petsky, Helen L; Cates, Chris J; Kew, Kayleigh M; Chang, Anne B

2018-06-01

Asthma guidelines guide health practitioners to adjust treatments to the minimum level required for asthma control. As many people with asthma have an eosinophilic endotype, tailoring asthma medications based on airway eosinophilic levels (sputum eosinophils or exhaled nitric oxide, FeNO) may improve asthma outcomes. To synthesise the evidence from our updated Cochrane systematic reviews, for tailoring asthma medication based on eosinophilic inflammatory markers (sputum analysis and FeNO) for improving asthma-related outcomes in children and adults. Cochrane reviews with standardised searches up to February 2017. The Cochrane reviews included randomised controlled comparisons of tailoring asthma medications based on sputum analysis or FeNO compared with controls (primarily clinical symptoms and/or spirometry/peak flow). The 16 included studies of FeNO-based management (seven in adults) and 6 of sputum-based management (five in adults) were clinically heterogeneous. On follow-up, participants randomised to the sputum eosinophils strategy (compared with controls) were significantly less likely to have exacerbations (62 vs 82/100 participants with ≥1 exacerbation; OR 0.36, 95% CI 0.21 to 0.62). For the FeNO strategy, the respective numbers were adults OR 0.60 (95% CI 0.43 to 0.84) and children 0.58 (95% CI 0.45 to 0.75). However, there were no significant group differences for either strategy on daily inhaled corticosteroids dose (at end of study), asthma control or lung function. Adjusting treatment based on airway eosinophilic markers reduced the likelihood of asthma exacerbations but had no significant impact on asthma control or lung function. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effective antigen presentation to helper T cells by human eosinophils.

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Farhan, Ruhaifah K; Vickers, Mark A; Ghaemmaghami, Amir M; Hall, Andrew M; Barker, Robert N; Walsh, Garry M

2016-12-01

Although eosinophils are inflammatory cells, there is increasing attention on their immunomodulatory roles. For example, murine eosinophils can present antigen to CD4 + T helper (Th) cells, but it remains unclear whether human eosinophils also have this ability. This study determined whether human eosinophils present a range of antigens, including allergens, to activate Th cells, and characterized their expression of MHC class II and co-stimulatory molecules required for effective presentation. Human peripheral blood eosinophils purified from non-allergic donors were pulsed with the antigens house dust mite extract (HDM), Timothy Grass extract (TG) or Mycobacterium tuberculosis purified protein derivative (PPD), before co-culture with autologous CD4 + Th cells. Proliferative and cytokine responses were measured, with eosinophil expression of HLA-DR/DP/DQ and the co-stimulatory molecules CD40, CD80 and CD86 determined by flow cytometry. Eosinophils pulsed with HDM, TG or PPD drove Th cell proliferation, with the response strength dependent on antigen concentration. The cytokine responses varied with donor and antigen, and were not biased towards any particular Th subset, often including combinations of pro- and anti-inflammatory cytokines. Eosinophils up-regulated surface expression of HLA-DR/DP/DQ, CD80, CD86 and CD40 in culture, increases that were sustained over 5 days when incubated with antigens, including HDM, or the major allergens it contains, Der p I or Der p II. Human eosinophils can, therefore, act as effective antigen-presenting cells to stimulate varied Th cell responses against a panel of antigens including HDM, TG or PPD, an ability that may help to determine the development of allergic disease. © 2016 John Wiley & Sons Ltd.

Re-defining the Unique Roles for Eosinophils in Allergic Respiratory Inflammation

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Jacobsen, Elizabeth A.; Lee, Nancy A.; Lee, James J.

2014-01-01

Summary The role of eosinophils in the progression and resolution of allergic respiratory inflammation is poorly defined despite the commonality of their presence and in some cases their use as a biomarker for disease severity and/or symptom control. However, this ambiguity belies the wealth of insights that have recently been gained through the use of eosinophil-deficient/attenuated strains of mice that have demonstrated novel immunoregulatory and remodeling/repair functions for these cells in the lung following allergen provocation. Specifically, studies of eosinophil-deficient mice suggest that eosinophils contribute to events occurring in the lungs following allergen provocation at several key moments: (i) The initiating phase of events leading to Th2-polarized pulmonary inflammation, (ii) The suppression Th1/Th17 pathways in lung draining lymph nodes, (iii) The recruitment of effector Th2 T cells to the lung, and finally (iv) Mechanisms of inflammatory resolution that re-establish pulmonary homeostasis. These suggested functions have recently been confirmed and expanded upon using allergen provocation of an inducible eosinophil-deficient strain of mice (iPHIL) that demonstrated an eosinophil-dependent mechanism(s) leading to Th2 dominated immune responses in the presence of eosinophils in contrast to neutrophilic as well as mixed Th1/Th17/Th2 variant phenotypes in the absence of eosinophils. These findings highlighted that eosinophils are not exclusively downstream mediators controlled by T cells, dendritic cells (DC), and/or innate lymphocytic cells (ILC2). Instead, eosinophils appear to be more aptly described as significant contributors in complex interrelated pathways that lead to pulmonary inflammation and subsequently promote resolution and the re-establishment of homeostatic baseline. In this review we summarize and put into the context the evolving hypotheses that are now expanding our understanding of the roles eosinophils likely have in the lung

Eosinophilic Pleural Effusion: A Rare Manifestation of Hypereosinophilic Syndrome

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Ndubuisi C. Okafor

2009-01-01

Full Text Available Several causes of eosinophilic pleural effusions have been described with malignancy being the commonest cause. Hypereosinophilic syndrome (HES is a rare disease and very few cases have been reported of HES presenting as eosinophilic pleural effusion (EPE. We report a case of a 26-year-old male who presented with shortness of breath. He had bilateral pleural effusions, generalized lymphadenopathy, splenomegaly, and leukocytosis with marked peripheral blood eosinophilia. The pleural fluid was exudative, with 25%–30% eosinophilis, and absence of neoplastic cells. Hypereosinophilic syndrome was diagnosed after other causes of eosinophilia were excluded. He continued to be dyspneic with persistent accumulation of eosinophilic pleural fluid, even after his peripheral eosinophil count had normalized in response to treatment. This patient represents a very unusual presentation of HES with dyspnea and pleural effusions and demonstrates that treatment based on response of peripheral eosinophil counts, as is currently recommended, may not always be clinically adequate.

Eosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation.

LENUS (Irish Health Repository)

Walsh, Marie-Therese

2011-11-01

Eosinophils exert many of their inflammatory effects in allergic disorders through the degranulation and release of intracellular mediators, including a set of cationic granule proteins that include eosinophil peroxidase. Studies suggest that eosinophils are involved in remodeling. In previous studies, we showed that eosinophil granule proteins activate mitogen-activated protein kinase signaling. In this study, we investigated the receptor mediating eosinophil peroxidase-induced signaling and downstream effects. Human cholinergic neuroblastoma IMR32 and murine melanoma B16.F10 cultures, real-time polymerase chain reaction, immunoprecipitations, and Western blotting were used in the study. We showed that eosinophil peroxidase caused a sustained increase in both the expression of epidermal growth factor-2 (HER2) and its phosphorylation at tyrosine 1248, with the consequent activation of extracellular-regulated kinase 1\\/2. This, in turn, promoted a focal adhesion kinase-dependent egress of the cyclin-dependent kinase inhibitor p27(kip) from the nucleus to the cytoplasm. Eosinophil peroxidase induced a HER2-dependent up-regulation of cell proliferation, indicated by an up-regulation of the nuclear proliferation marker Ki67. This study identifies HER2 as a novel mediator of eosinophil peroxidase signaling. The results show that eosinophil peroxidase, at noncytotoxic levels, can drive cell-cycle progression and proliferation, and contribute to tissue remodeling and cell turnover in airway disease. Because eosinophils are a feature of many cancers, these findings also suggest a role for eosinophils in tumorigenesis.

Eosinophilia in a patient with cyclical vomiting: a case report

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Fitzgerald S Matthew

2004-05-01

Full Text Available Abstract Background Eosinophilic gastritis is related to eosinophilic gastroenteritis, varying only in regards to the extent of disease and small bowel involvement. Common symptoms reported are similar to our patient's including: abdominal pain, epigastric pain, anorexia, bloating, weight loss, diarrhea, ankle edema, dysphagia, melaena and postprandial nausea and vomiting. Microscopic features of eosinophilic infiltration usually occur in the lamina propria or submucosa with perivascular aggregates. The disease is likely mediated by eosinophils activated by various cytokines and chemokines. Therapy centers around the use of immunosuppressive agents and dietary therapy if food allergy is a factor. Case presentation The patient is a 31 year old Caucasian female with a past medical history significant for ulcerative colitis. She presented with recurrent bouts of vomiting, abdominal pain and chest discomfort of 11 months duration. The bouts of vomiting had been reoccurring every 7–10 days, with each episode lasting for 1–3 days. This was associated with extreme weakness and cachexia. Gastric biopsies revealed intense eosinophilic infiltration. The patient responded to glucocorticoids and azathioprine. The differential diagnosis and molecular pathogenesis of eosinophilic gastritis as well as the molecular effects of glucocorticoids in eosinophilic disorders are discussed. Conclusions The patient responded to a combination of glucocorticosteroids and azathioprine with decreased eosinophilia and symptoms. It is likely that eosinophil-active cytokines such as interleukin-3 (IL-3, granulocyte macrophage colony stimulating factor (GM-CSF and IL-5 play pivotal roles in this disease. Chemokines such as eotaxin may be involved in eosinophil recruitment. These mediators are downregulated or inhibited by the use of immunosuppressive medications.

Proton channel HVCN1 is required for effector functions of mouse eosinophils

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2013-01-01

Background Proton currents are required for optimal respiratory burst in phagocytes. Recently, HVCN1 was identified as the molecule required for the voltage-gated proton channel activity associated with the respiratory burst in neutrophils. Although there are similarities between eosinophils and neutrophils regarding their mechanism for respiratory burst, the role of proton channels in eosinophil functions has not been fully understood. Results In the present study, we first identified the expression of the proton channel HVCN1 in mouse eosinophils. Furthermore, using HVCN1-deficient eosinophils, we demonstrated important cell-specific effector functions for HVCN1. Similar to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils produced significantly less reactive oxygen species (ROS) upon phorbol myristate acetate (PMA) stimulation compared with WT eosinophils. In contrast to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils did not show impaired calcium mobilization or migration ability compared with wild-type (WT) cells. Uniquely, HVCN1-deficient eosinophils underwent significantly increased cell death induced by PMA stimulation compared with WT eosinophils. The increased cell death was dependent on NADPH oxidase activation, and correlated with the failure of HVCN1-deficient cells to maintain membrane polarization and intracellular pH in the physiological range upon activation. Conclusions Eosinophils require proton channel HVCN1 for optimal ROS generation and prevention of activation-induced cell death. PMID:23705768

Increased eosinophil activity in acute Plasmodium falciparum infection - association with cerebral malaria

DEFF Research Database (Denmark)

Kurtzhals, J A; Reimert, C M; Tette, E

1998-01-01

To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven...... of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness...... followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM...

Eosinophilic granuloma of the mandibular condyle

International Nuclear Information System (INIS)

Huh, Kyung Hoe; Yi, Won Jin; Oh, Sung Won; Lee, Sam Sun; Choi, Mun Kyung

2008-01-01

The present study reports a case of eosinophilic granuloma of the mandibular condyle. Eosinophilic granulomas on the mandibular condyle are very rare, but there are several common clinical and radiographic presentations. The clinical presentations involve swelling on preauricular area, limitation of opening, TMJ pain, etc. The radiographic presentations involve radiolucent lytic condylar lesion with or without pathologic fracture. Sometimes new bone formations are observed. The purpose of the article is to add new cases to the literatures.

Eosinophilic granuloma of the mandibular condyle

Energy Technology Data Exchange (ETDEWEB)

Huh, Kyung Hoe; Yi, Won Jin; Oh, Sung Won; Lee, Sam Sun [Department of Oral and Maxillofacial Radiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Choi, Mun Kyung [Department of Oral and Maxillofacial Surgery, College of Medicine, Inje University Sanggye Paik Hospital, Seoul (Korea, Republic of)

2008-03-15

The present study reports a case of eosinophilic granuloma of the mandibular condyle. Eosinophilic granulomas on the mandibular condyle are very rare, but there are several common clinical and radiographic presentations. The clinical presentations involve swelling on preauricular area, limitation of opening, TMJ pain, etc. The radiographic presentations involve radiolucent lytic condylar lesion with or without pathologic fracture. Sometimes new bone formations are observed. The purpose of the article is to add new cases to the literatures.

Eosinophilic cystitis in a 3-year-old boy

International Nuclear Information System (INIS)

Breysem, L.; Smet, M.H.; Gordts, H.; Marchal, G.

1991-01-01

Eosinophilic cystitis is a rare in children; it also affects adults. Clinical manifestations are variable. The diagnosis can be confirmed by cystoscopy and biopsy, both rather invasive procedures, especially in younger patients. We report a 3-year-old boy with eosinophilic cystitis. The most important radiological finding was marked thickening of the bladder wall, documented on ultrasound, cystography and CT. The CT findings of eosinophilic cystitis have, to the best of our knowledge, not been reported before. In addition to ultrasound and cystography, CT clearly demonstrates extension of the inflammatory process into the perivesical tissues. (orig.)

Eosinophilic Myocarditis due to Toxocariasis: Not a Rare Cause

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Shunichi Shibazaki

2016-01-01

Full Text Available Myocarditis is a clinically important disease because of the high mortality. From the perspective of treatment strategy, eosinophilic myocarditis should be distinguished from other types of myocarditis. Toxocariasis, caused by Toxocara canis or Toxocara cati, is known as a cause of eosinophilic myocarditis but is considered rare. As it is an unpopular disease, eosinophilic myocarditis due to toxocariasis may be underdiagnosed. We experienced two cases of eosinophilic myocarditis due to toxocariasis from different geographical areas in quick succession between 2013 and 2014. Case 1 is 32-year-old man. Case 2 is 66-year-old woman. In both cases, diagnosis was done by endomyocardial biopsy and IgG-ELISA against Toxocara excretory-secretory antigen. Only a corticosteroid was used in Case  1, whereas a corticosteroid and albendazole were used in Case  2 as induction therapy. Both patients recovered. Albendazole was also used in Case  1 to prevent recurrence after induction therapy. Eosinophilic myocarditis by toxocariasis may in actuality not be a rare disease, and corticosteroid is an effective drug as induction therapy even before use of albendazole.

Detection of eosinophil cationic protein (ECP) by an enzyme-linked immunosorbent assay

DEFF Research Database (Denmark)

Reimert, C M; Venge, P; Kharazmi, A

1991-01-01

Eosinophil cationic protein (ECP) is a highly basic and potent cytotoxic single-chain zinc-containing protein present in the granules of the eosinophilic granulocytes. ECP appears to be involved in defence against parasites and in the tissue damage seen in subjects with allergic and inflammatory...... disease. To investigate ECP release from in vitro activated human eosinophils and to study the involvement of eosinophils in health and disease, we have developed a sensitive and specific enzyme immunoassay. ECP was purified from normal human peripheral blood eosinophils and polyclonal antibodies to ECP...

In vivo activation of equine eosinophils and neutrophils by experimental Strongylus vulgaris infections.

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Dennis, V A; Klei, T R; Chapman, M R; Jeffers, G W

1988-12-01

Eosinophils and neutrophils from ponies with Strongylus vulgaris-induced eosinophilia (eosinophilic ponies; activated eosinophils and neutrophils) were assayed in vitro for chemotactic and chemokinetic responses to zymosan-activated serum (ZAS) using the filter system in Boyden chambers, for Fc and complement (C) receptors using the EA and EAC-rosette assays, respectively, and for phagocytic and bactericidal activities using opsonized Escherichia coli and the acridine orange method. The responses of activated eosinophils and neutrophils in the above assays were compared with those of eosinophils and neutrophils from S. vulgaris-naive ponies without eosinophilia (noneosinophilic ponies; nonactivated eosinophils and neutrophils). Differences in cell density following centrifugation in a continuous Percoll gradient were used to further characterize the heterogeneity of activated eosinophils and neutrophils. Activated and nonactivated eosinophils demonstrated similar chemotactic responses to ZAS while activated and nonactivated neutrophils demonstrated similar chemokinetic responses to ZAS. A higher percentage of activated eosinophils and neutrophils expressed Fc and C receptors compared with nonactivated cells (P less than 0.05). Generally, higher percentages of eosinophils and neutrophils expressed C than Fc receptors. However, the percentage of neutrophils with both receptors was higher than that of eosinophils. Phagocytosis and killing of E. coli by either type of eosinophil were not consistently observed. Both activated and nonactivated neutrophils phagocytized E. coli and significant differences between the two cell types were not observed. The bacterial activity, however, of activated neutrophils was significantly greater than that obtained using nonactivated neutrophils (P less than 0.05). Activated eosinophils and neutrophils were both separated into two distinct fractions based on differences in cell densities. A higher percentage of band 2 eosinophils

Omalizumab in patients with eosinophilic granulomatosis with polyangiitis: a 36-month follow-up study.

Science.gov (United States)

Detoraki, Aikaterini; Di Capua, Lorena; Varricchi, Gilda; Genovese, Arturo; Marone, Gianni; Spadaro, Giuseppe

2016-01-01

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis characterized by asthma and blood eosinophilia, with the lung being the organ most frequently affected. Oral glucocorticoids and/or immunosuppressive drugs are the mainstay therapy of EGPA. Occasional reports suggest that EGPA patients can be treated with omalizumab in addition to conventional therapy to achieve asthma control. To investigate the long-term effects of omalizumab in patients with EGPA and asthma (2 females, 3 males, age 41-64 years), we carried out a 36-month follow-up observational study. At the time of enrollment, the patients were on maintenance therapy and had moderate to severe allergic asthma, eosinophilia and rhinosinusitis. Mononeuropathy/polyneuropathy and/or histological evidence of tissue eosinophilic infiltration were also present. Patients were treated with omalizumab (300-600 mg s.c. every 2-4 weeks) as add-on therapy to prednisone, inhaled steroids and bronchodilators. During omalizumab treatment, spirometry, the asthma control test (ACT) score and eosinophilia were evaluated, and prednisone dosage was recorded. During the 36 months of omalizumab treatment asthma progressively improved as indicated by spirometry and the ACT score. Eosinophilia progressively decreased. The oral prednisone dose was reduced or withdrawn during treatment. No adverse events were recorded. In patients with EGPA and moderate to severe allergic asthma, omalizumab can be beneficial and safe. It enables corticosteroid tapering while decreasing eosinophilia and improving asthma symptoms over 36 months.

Inhibition of aldose reductase prevents experimental allergic airway inflammation in mice.

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Umesh C S Yadav

2009-08-01

Full Text Available The bronchial asthma, a clinical complication of persistent inflammation of the airway and subsequent airway hyper-responsiveness, is a leading cause of morbidity and mortality in critically ill patients. Several studies have shown that oxidative stress plays a key role in initiation as well as amplification of inflammation in airways. However, still there are no good anti-oxidant strategies available for therapeutic intervention in asthma pathogenesis. Most recent studies suggest that polyol pathway enzyme, aldose reductase (AR, contributes to the pathogenesis of oxidative stress-induced inflammation by affecting the NF-kappaB-dependent expression of cytokines and chemokines and therefore inhibitors of AR could be anti-inflammatory. Since inhibitors of AR have already gone through phase-III clinical studies for diabetic complications and found to be safe, our hypothesis is that AR inhibitors could be novel therapeutic drugs for the prevention and treatment of asthma. Hence, we investigated the efficacy of AR inhibition in the prevention of allergic responses to a common natural airborne allergen, ragweed pollen that leads to airway inflammation and hyper-responsiveness in a murine model of asthma.Primary Human Small Airway Epithelial Cells (SAEC were used to investigate the in vitro effects of AR inhibition on ragweed pollen extract (RWE-induced cytotoxic and inflammatory signals. Our results indicate that inhibition of AR prevents RWE -induced apoptotic cell death as measured by annexin-v staining, increase in the activation of NF-kappaB and expression of inflammatory markers such as inducible nitric oxide synthase (iNOS, cycloxygenase (COX-2, Prostaglandin (PG E(2, IL-6 and IL-8. Further, BALB/c mice were sensitized with endotoxin-free RWE in the absence and presence of AR inhibitor and followed by evaluation of perivascular and peribronchial inflammation, mucin production, eosinophils infiltration and airway hyperresponsiveness. Our results

Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.

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Sugawara, Reiko; Lee, Eun-Jung; Jang, Min Seong; Jeun, Eun-Ji; Hong, Chun-Pyo; Kim, Jung-Hwan; Park, Areum; Yun, Chang Ho; Hong, Sung-Wook; Kim, You-Me; Seoh, Ju-Young; Jung, YunJae; Surh, Charles D; Miyasaka, Masayuki; Yang, Bo-Gie; Jang, Myoung Ho

2016-04-04

Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+)T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra. © 2016 Sugawara et al.

Eosinophilic pleural effusion: incidence, etiology and prognostic significance.

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Ferreiro, Lucía; San José, Esther; González-Barcala, Francisco Javier; Alvarez-Dobaño, José Manuel; Golpe, Antonio; Gude, Francisco; Anchorena, Christian; Pereyra, Marco F; Zamarrón, Carlos; Valdés, Luis

2011-10-01

Eosinophilic pleural effusion (EPE) has been associated with less risk for malignancy with a potential causal relationship with the presence of air and/or blood in the pleural space. However, these theories have fallen by the wayside in the light of recent publications. To determine the incidence and etiology of EPE and to observe whether the eosinophils in the pleural liquid (PL) increase in successive thoracocenteses. We analyzed 730 PL samples from 605 patients hospitalized between January 2004 and December 2010. We identified 55 samples with EPE from 50 patients (8.3%). The most frequent etiologies of EPE were: unknown (36%) and neoplasm (30%). There were no significant differences in the incidence of neoplasms between the non-eosinophilic pleural effusions (non-EPE) (25.9%) and the EPE (30%) (p=0.533). One hundred patients (16.5%) underwent a second thoracocentesis. Out of the 9 who had EPE in the first, 6 maintained EPE in the second. Out of the 91 with non-EPE in the first thoracocentesis, 8 (8.8%) had EPE in the repeat thoracocentesis. The percentage of eosinophils did not increase in the successive thoracocenteses (p=0.427). In the EPE, a significant correlation was found between the number of hematites and eosinophils in the PL (r=0.563; p=0.000). An EPE cannot be considered an indicator of benignancy, therefore it should be studied as any other pleural effusion. The number of eosinophils does not seem to increase with the of repetition of thoracocentesis and, lastly, the presence of blood in the PL could explain the existence of EPE. Copyright © 2011 SEPAR. Published by Elsevier Espana. All rights reserved.

Genetics of eosinophilic esophagitis.

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Kottyan, L C; Rothenberg, M E

2017-05-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches.

Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

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Withers, Sarah B.; Forman, Ruth; Meza-Perez, Selene

2017-01-01

Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils...... in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability...... of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source...

A method for rapid testing of the photosynthesis-inhibiting activity of herbicides by leaf disk infiltration

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Krzysztof Bielecki

2013-12-01

Full Text Available A method for rapid detection of photosynthesis inhibitors in low concentration (0.25-1.25 ppm was developed. The experiments were performed on disks cut from young bean leaves. The disks were infiltrated with solutions of the tested compounds and placed at the bottom of a crystallizer containing an acidic sodium carbonate solution and then illuminated. The toxicity of the tested substance was measured as the number of disks corning to the surface. It was found that linuron, monolinuron, metoksuron, atrazine and prometrine inhibited floating of the disks, whereas 2,4,5-T, MCPA and chlorpropham gave no effect. This confirms the specificity of the test which is appropriate for determining the phytotoxicity of typical photosynthesis inhibitors.

Eosinophil count is positively correlated with coronary artery calcification

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Tanaka, Muhei; Fukui, Michiaki; Yamasaki, Masahiro; Hasegawa, Goji; Oda, Yohei; Nakamura, Naoto; Tomiyasu, Ki-ichiro; Akabame, Satoshi; Nakano, Koji

2012-01-01

Recent studies suggested that allergic disorders and increased eosinophil count were associated with atherosclerosis. The purpose of this study was to assess the relationship between eosinophil count and coronary artery calcification (CAC). We performed a cross-sectional study in 1363 consecutive participants with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAC score determined by multislice CT and peripheral eosinophil count as well as major cardiovascular risk factors, including age, body mass index, smoking status, hypertension, dyslipidemia, diabetes mellitus (DM), high-sensitivity C-reactive protein and estimated glomerular filtration rate (eGFR). Sex (P=0.0004), hypertension (P=0.0002), dyslipidemia (P=0.0004) and DM (P=0.0061) were associated with log (CAC+1), respectively. Positive correlations were found between log (CAC+1), and age (r=0.325, P<0.0001) and eosinophil count (r=0.165, P<0.0001). Negative correlations were found between log (CAC+1) and eGFR (r=-0.166, P<0.0001). Multivariate linear regression analysis demonstrated that age (β=0.314, P<0.0001), sex (β=0.124, P<0.0001), hypertension (β=0.084, P=0.0008), DM (β=0.108, P<0.0001), eGFR (β=-0.079, P=0.0021) and eosinophil count (β=0.147, P<0.0001) were independent determinants of log (CAC+1). In conclusion, eosinophil count correlated positively with CAC in participants with clinical suspicion of CHD. (author)

Eosinophilic granuloma in the anterior mandible mimicking radicular cyst

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Lee, Byung Do; Lee, Wan; Lee, Jun; Son, Hyun Jin

2013-01-01

Eosinophilic granuloma is a common expression of Langerhans cell histiocytosis and corresponds with typical bone lesions. The radiographic appearance of eosinophilic granuloma in the jaw is variable and not specific. It may resemble periodontitis, radicular cyst, or malignancies. The purpose of this report is to describe the characteristic radiographic features of eosinophilic granuloma of a 39-year-old male. The lesion in the anterior mandible was first diagnosed as radicular cyst because the radiographic findings were ovoid radiolucent lesion with well-defined border. However, careful interpretation revealed a non-corticated border and floating tooth appearance that were the characteristic radiographic features for the differential diagnosis. Early clinical signs of eosinophilic granuloma can occur in the jaw and a bony destructive lesion might be mistaken for periodontitis or an odontogenic cystic lesion; therefore, careful interpretation of radiographs should be emphasized.

Eosinophilic granuloma in the anterior mandible mimicking radicular cyst

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Lee, Byung Do; Lee, Wan; Lee, Jun [College of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Son, Hyun Jin [Dept. of Pathology, School of Medicine, Eulji University, Daejeon (Korea, Republic of)

2013-06-15

Eosinophilic granuloma is a common expression of Langerhans cell histiocytosis and corresponds with typical bone lesions. The radiographic appearance of eosinophilic granuloma in the jaw is variable and not specific. It may resemble periodontitis, radicular cyst, or malignancies. The purpose of this report is to describe the characteristic radiographic features of eosinophilic granuloma of a 39-year-old male. The lesion in the anterior mandible was first diagnosed as radicular cyst because the radiographic findings were ovoid radiolucent lesion with well-defined border. However, careful interpretation revealed a non-corticated border and floating tooth appearance that were the characteristic radiographic features for the differential diagnosis. Early clinical signs of eosinophilic granuloma can occur in the jaw and a bony destructive lesion might be mistaken for periodontitis or an odontogenic cystic lesion; therefore, careful interpretation of radiographs should be emphasized.

The effects of TYB-2285 and its metabolites on eosinophil adhesion to tumor necrosis factor α-stimulated human umbilical vein endothelial cells

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Takanari Tominaga

1996-01-01

The results of the present study demonstrate that TYB-2285 and its metabolites selectively inhibit the adhesion of eosinophils to HUVECs stimulated with TNF-α and also suggest that TYB-2285, TC-286 and TC-326 might block the VLA-4/VCAM-1 pathway selectively.

Eosinophilic Esophagitis (EoE)

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... excluded usually include dairy, egg, wheat, soy, peanut, tree nuts and fish/shellfish. These diets have been ... minorities » IgE ab to minor milk proteins may identify the proteins that are relevant to eosinophilic esophagitis » ...

Pediatric eosinophilic esophagitis: radiologic findings with pathologic correlation

International Nuclear Information System (INIS)

Binkovitz, Larry A.; Lorenz, Emily A.; Di Lorenzo, Carlo; Kahwash, Samir

2010-01-01

Eosinophilic esophagitis is increasingly recognized as a cause of dysphagia or food impaction in pediatric patients. It has a high male predominance and is often associated with a history of allergy or asthma. To correlate fluoroscopic findings in eosinophilic esophagitis with the endoscopic and histologic findings. We retrospectively reviewed the upper gastrointestinal (UGI) findings of eosinophilic esophagitis and correlated them with the clinical, endoscopic and histologic findings in a series of 17 children (12 boys, 5 girls). UGI findings were normal in 12 children, including 4 who had a normal UGI exam after endoscopic disimpaction for an obstructing food bolus. Five children had strictures identified on UGI: one was demonstrated with endoscopy. This suggests that the impactions and strictures were due to an esophageal dysmotility rather than a fixed anatomic abnormality. Because the UGI findings are frequently normal in eosinophilic esophagitis, radiologists need to have a high index of suspicion for this disease. In children with a strong clinical history, especially impaction in the absence of an esophageal stricture, endoscopy and biopsy are indicated for further evaluation. (orig.)

Pediatric eosinophilic esophagitis: radiologic findings with pathologic correlation

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Binkovitz, Larry A. [Nationwide Children' s Hospital, Columbus, OH (United States); Mayo Clinic, Division of Pediatric Radiology, E-2, Rochester, MN (United States); Lorenz, Emily A. [Nationwide Children' s Hospital, Columbus, OH (United States); Di Lorenzo, Carlo [Nationwide Children' s Hospital, Department of Gastroenterology, Columbus, OH (United States); Kahwash, Samir [Nationwide Children' s Hospital, Department of Pathology, Columbus, OH (United States)

2010-05-15

Eosinophilic esophagitis is increasingly recognized as a cause of dysphagia or food impaction in pediatric patients. It has a high male predominance and is often associated with a history of allergy or asthma. To correlate fluoroscopic findings in eosinophilic esophagitis with the endoscopic and histologic findings. We retrospectively reviewed the upper gastrointestinal (UGI) findings of eosinophilic esophagitis and correlated them with the clinical, endoscopic and histologic findings in a series of 17 children (12 boys, 5 girls). UGI findings were normal in 12 children, including 4 who had a normal UGI exam after endoscopic disimpaction for an obstructing food bolus. Five children had strictures identified on UGI: one was demonstrated with endoscopy. This suggests that the impactions and strictures were due to an esophageal dysmotility rather than a fixed anatomic abnormality. Because the UGI findings are frequently normal in eosinophilic esophagitis, radiologists need to have a high index of suspicion for this disease. In children with a strong clinical history, especially impaction in the absence of an esophageal stricture, endoscopy and biopsy are indicated for further evaluation. (orig.)

Isolation of Eosinophils from the Lamina Propria of the Murine Small Intestine.

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Berek, Claudia; Beller, Alexander; Chu, Van Trung

2016-01-01

Only recently has it become apparent that eosinophils play a crucial role in mucosal immune homeostasis. Although eosinophils are the main cellular component of the lamina propria of the gastrointestinal tract, they have often been overlooked because they express numerous markers, which are normally used to characterize macrophages and/or dendritic cells. To study their function in mucosal immunity, it is important to isolate them with high purity and viability. Here, we describe a protocol to purify eosinophils from the lamina propria of the murine small intestine. The method involves preparation of the small intestine, removal of epithelial cells and digestion of the lamina propria to release eosinophils. A protocol to sort eosinophils is included.

Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma

DEFF Research Database (Denmark)

Duong, MyLinh; Subbarao, Padmaja; Adelroth, Ellinor

2008-01-01

BACKGROUND: The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined. METHODS: Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double...... and sputum analysis were performed. RESULTS: Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated...... eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of eosinophilic groups in the magnitude of improvement in EIB was evident after the first...

Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease

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Vedel-Krogh, Signe; Nielsen, Sune F; Lange, Peter

2016-01-01

RATIONALE: Whether high blood eosinophils are associated with COPD exacerbations among individuals with COPD in the general population is largely unknown. OBJECTIVES: To test the hypothesis that high blood eosinophils predict COPD exacerbations. METHODS: Among 81,668 individuals from the Copenhagen...... General Population Study, we examined 7,225 with COPD based on spirometry. We recorded blood eosinophils at baseline and future COPD exacerbations longitudinally, defined as moderate (short-course treatment of systemic corticosteroids) or severe (hospitalization). We also assessed exacerbation risk...... in a subgroup of 203 COPD individuals with clinical COPD, defined as participants with ≥ 10 pack-years, FEV1

Eosinophilic Colitis: University of Minnesota Experience and Literature Review

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Wolfgang B. Gaertner

2011-01-01

Full Text Available Eosinophilic colitis is a rare form of primary eosinophilic gastrointestinal disease that is poorly understood. Neonates and young adults are more frequently affected. Clinical presentation is highly variable depending on the depth of inflammatory response (mucosal, transmural, or serosal. The pathophysiology of eosinophilic colitis is unclear but is suspected to be related to a hypersensitivity reaction given its correlation with other atopic disorders and clinical response to corticosteroid therapy. Diagnosis is that of exclusion and differential diagnoses are many because colonic tissue eosinophilia may occur with other colitides (parasitic, drug-induced, inflammatory bowel disease, and various connective tissue disorders. Similar to other eosinophilic gastrointestinal disorders, steroid-based therapy and diet modification achieve very good and durable responses. In this paper, we present our experience with this rare pathology. Five patients (3 pediatric and 2 adults presented with diarrhea and hematochezia. Mean age at presentation was 26 years. Mean duration of symptoms before pathologic diagnosis was 8 months. Mean eosinophil count per patient was 31 per high-power field. The pediatric patients responded very well to dietary modifications, with no recurrences. The adult patients were treated with steroids and did not respond. Overall mean followup was 22 (range, 2–48 months.

T Lymphocyte Inhibition by Tumor-Infiltrating Dendritic Cells Involves Ectonucleotidase CD39 but Not Arginase-1

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Malika Trad

2015-01-01

Full Text Available T lymphocytes activated by dendritic cells (DC which present tumor antigens play a key role in the antitumor immune response. However, in patients suffering from active cancer, DC are not efficient at initiating and supporting immune responses as they participate to T lymphocyte inhibition. DC in the tumor environment are functionally defective and exhibit a characteristic of immature phenotype, different to that of DC present in nonpathological conditions. The mechanistic bases underlying DC dysfunction in cancer responsible for the modulation of T-cell responses and tumor immune escape are still being investigated. Using two different mouse tumor models, we showed that tumor-infiltrating DC (TIDC are constitutively immunosuppressive, exhibit a semimature phenotype, and impair responder T lymphocyte proliferation and activation by a mechanism involving CD39 ectoenzyme.

Higher frequency of cholelithiasis in eosinophilic cholecystitis, an unusual finding

International Nuclear Information System (INIS)

Sarfraz, T.; Tariq, H.; Bashir, S.

2015-01-01

To determine the frequency of cholelithiasis in eosinophilic cholecystitis in our population. Study Design: Prospective descriptive study. Place and Duration of Study: Histopathology department, Combined Military Hospital (CMH), Peshawar (Pakistan) from Dec 2011 to Nov 2014. Material and Methods: Eighteen hundred (1800) cholecystectomy specimens were included in the study. The specimens which were properly fixed in 10% formalin were included in the specimen, while poorly fixed and autolysed specimens were excluded. The specimens were examined grossly, measured and block selection was done. The slides made were examined under light microscope by one histopathologist and findings were analyzed. Results: Out of 1800 cholecystectomy specimens, 25 cases (1.38%) were diagnosed as eosinophilic cholecystitis. Out of these 25 cases, 20 (80%) were females having an age range of 30-50 years, while 5 (20%) were males with an age range of 35-55 years. Out of these 25 cases of eosinophilic cholecystitis, 22 (88%) were having cholelithiasis, while 3 (12%) were acalculous eosiniophilic cholecystitis. Conclusion: Eosinophilic cholecystitis in our population is mostly calculous which is very significant finding contrary to data given in western literature, where most of eosinophilic cholecystitis is aclculous. This needs further evaluation to determine any genetic, geographic, environmental, dietary, microbiological or any other factor responsible in etiopathogenesis of calculous eosinophilic cholecystitis in our population, which could be helpful in prevention and management of this disease. (author)

Point-of-care blood eosinophil count in a severe asthma clinic setting.

Science.gov (United States)

Heffler, Enrico; Terranova, Giovanni; Chessari, Carlo; Frazzetto, Valentina; Crimi, Claudia; Fichera, Silvia; Picardi, Giuseppe; Nicolosi, Giuliana; Porto, Morena; Intravaia, Rossella; Crimi, Nunzio

2017-07-01

One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers. A significant correlation between blood eosinophils assessed by the 2 devices was found (R 2  = 0.854, P asthma and the ELEN index, a composite score useful to predict sputum eosinophilia. The results of our study contribute to the validation of a point-of-care device to assess blood eosinophils and open the possibility of using this device for the management of severe asthma management. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The plant extract Isatis tinctoria L. extract (ITE) inhibits allergen-induced airway inflammation and hyperreactivity in mice.

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Brattström, A; Schapowal, A; Kamal, M A; Maillet, I; Ryffel, B; Moser, R

2010-07-01

The herbal Isatis tinctoria extract (ITE) inhibits the inducible isoform of cyclooxygenase (COX-2) as well as lipoxygenase (5-LOX) and therefore possesses anti-inflammatory properties. The extract might also be useful in allergic airway diseases which are characterized by chronic inflammation. ITE obtained from leaves by supercritical carbon dioxide extraction was investigated in ovalbumin (OVA) immunised BALB/c mice given intranasally together with antigen challenge in the murine model of allergic airway disease (asthma) with the analysis of the inflammatory and immune parameters in the lung. ITE given with the antigen challenge inhibited in a dose related manner the allergic response. ITE diminished airway hyperresponsiveness (AHR) and eosinophil recruitment into the bronchoalveolar lavage (BAL) fluid upon allergen challenge, but had no effect in the saline control mice. Eosinophil recruitment was further assessed in the lung by eosinophil peroxidase (EPO) activity at a dose of 30 microg ITE per mouse. Microscopic investigations revealed less inflammation, eosinophil recruitment and mucus hyperproduction in the lung in a dose related manner. Diminution of AHR and inflammation was associated with reduced IL-4, IL-5, and RANTES production in the BAL fluid at the 30 microg ITE dose, while OVA specific IgE and eotaxin serum levels remained unchanged. ITE, which has been reported inhibiting COX-2 and 5-LOX, reduced allergic airway inflammation and AHR by inhibiting the production of the Th2 cytokines IL-4 and IL-5, and RANTES. (c) 2009 Elsevier GmbH. All rights reserved.

Phenotypic and Functional Properties of Tumor-Infiltrating Regulatory T Cells

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Gap Ryol Lee

2017-01-01

Full Text Available Regulatory T (Treg cells maintain immune homeostasis by suppressing excessive immune responses. Treg cells induce tolerance against self- and foreign antigens, thus preventing autoimmunity, allergy, graft rejection, and fetus rejection during pregnancy. However, Treg cells also infiltrate into tumors and inhibit antitumor immune responses, thus inhibiting anticancer therapy. Depleting whole Treg cell populations in the body to enhance anticancer treatments will produce deleterious autoimmune diseases. Therefore, understanding the precise nature of tumor-infiltrating Treg cells is essential for effectively targeting Treg cells in tumors. This review summarizes recent results relating to Treg cells in the tumor microenvironment, with particular emphasis on their accumulation, phenotypic, and functional properties, and targeting to enhance the efficacy of anticancer treatment.

The Role and Immunobiology of Eosinophils in the Respiratory System: a Comprehensive Review.

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Eng, Stephanie S; DeFelice, Magee L

2016-04-01

The eosinophil is a fully delineated granulocyte that disseminates throughout the bloodstream to end-organs after complete maturation in the bone marrow. While the presence of eosinophils is not uncommon even in healthy individuals, these granulocytes play a central role in inflammation and allergic processes. Normally appearing in smaller numbers, higher levels of eosinophils in the peripheral blood or certain tissues typically signal a pathologic process. Eosinophils confer a beneficial effect on the host by enhancing immunity against molds and viruses. However, tissue-specific elevation of eosinophils, particularly in the respiratory system, can cause a variety of short-term symptoms and may lead to long-term sequelae. Eosinophils often play a role in more commonly encountered disease processes, such as asthma and allergic responses in the upper respiratory tract. They are also integral in the pathology of less common diseases including eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and drug reaction with eosinophilia and systemic symptoms. They can be seen in neoplastic disorders or occupational exposures as well. The involvement of eosinophils in pulmonary disease processes can affect the method of diagnosis and the selection of treatment modalities. By analyzing the complex interaction between the eosinophil and its environment, which includes signaling molecules and tissues, different therapies have been discovered and created in order to target disease processes at a cellular level. Innovative treatments such as mepolizumab and benralizumab will be discussed. The purpose of this article is to further explore the topic of eosinophilic presence, activity, and pathology in the respiratory tract, as well as discuss current and future treatment options through a detailed literature review.

IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells.

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Hashiguchi, Masaaki; Kashiwakura, Yuji; Kojima, Hidefumi; Kobayashi, Ayano; Kanno, Yumiko; Kobata, Tetsuji

2015-03-01

Eosinophils are multifunctional leukocytes involved in allergic reactions as well as adipose tissue regulation. IL-5 is required for eosinophil survival; however, the in vivo mechanisms of eosinophil regulation are not fully understood. A tg mouse model with il5 promoter-driven EGFP expression was established for detecting the IL-5-producing cells in vivo. Il5-egfp tg mice expressed high levels of EGFP in gonadal adipose tissue (GAT) cells. EGFP(+) cells in GAT were mainly group 2 innate lymphoid cells (ILCs). IL-33 preferentially expanded EGFP(+) cells and eosinophils in GAT in vivo. EGFP(+) ILCs were found to upregulate prg2 mRNA expression in GAT eosinophils. These results demonstrate that ILCs activate eosinophils in GAT. The blockage of IL-33Rα, on the other hand, did not impair EGFP(+) ILC numbers but did impair eosinophil numbers in vivo. GAT eosinophils expressed IL-33Rα and IL-33 expanded eosinophil numbers in CD90(+) cell-depleted mice. IL-33 was further observed to induce the expression of retnla and epx mRNA in eosinophils. These findings demonstrate that IL-33 directly activates eosinophils in GAT, and together with our other findings described above, our findings show that IL-33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC-mediated pathway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

5-Lipoxygenase-Dependent Recruitment of Neutrophils and Macrophages by Eotaxin-Stimulated Murine Eosinophils

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Ricardo Alves Luz

2014-01-01

Full Text Available The roles of eosinophils in antimicrobial defense remain incompletely understood. In ovalbumin-sensitized mice, eosinophils are selectively recruited to the peritoneal cavity by antigen, eotaxin, or leukotriene(LTB4, a 5-lipoxygenase (5-LO metabolite. 5-LO blockade prevents responses to both antigen and eotaxin. We examined responses to eotaxin in the absence of sensitization and their dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX; eosinophil-deficient GATA-1 were injected i.p. with eotaxin, eosinophils, or both, and leukocyte accumulation was quantified up to 24 h. Significant recruitment of eosinophils by eotaxin in BALB/c, up to 24 h, was accompanied by much larger numbers of recruited neutrophils and monocytes/macrophages. These effects were abolished by eotaxin neutralization and 5-LO-activating protein inhibitor MK886. In ALOX (but not PAS mice, eotaxin recruitment was abolished for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited neither neutrophils nor macrophages. Transfer of eosinophils cultured from bone-marrow of BALB/c donors, or from ALOX donors, into GATA-1 mutant recipients, i.p., restored eotaxin recruitment of neutrophils and showed that the critical step dependent on 5-LO is the initial recruitment of eosinophils by eotaxin, not the secondary neutrophil accumulation. Eosinophil-dependent recruitment of neutrophils in naive BALB/c mice was associated with increased binding of bacteria.

Diffuse alopecia areata is associated with intense inflammatory infiltration and CD8+ T cells in hair loss regions and an increase in serum IgE level

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Ying Zhao

2012-01-01

Full Text Available Background: Mechanism leading to an abrupt hair loss in diffuse alopecia areata (AA remains unclear. Aims: To explore the characteristics of diffuse AA and possible factors involved in its pathogenesis. Methods: Clinical and laboratory data of 17 diffuse AA patients and 37 patchy AA patients were analyzed retrospectively. Serum IgE level was evaluated in all diffuse and patchy AA patients, as well as 27 healthy subjects without hair loss to serve as normal control. Univariate analysis was performed using Fisher′s exact test and Wilcoxon rank-sum test. Associations between inflammatory cell infiltration and laboratory values were analyzed using Spearman rank correlation test. Results: The mean age of patients with diffuse AA was 27 years with a mean disease duration of 1.77 months. All of them presented in spring or summer with an acute onset of diffuse hair loss preceded by higher incidence of scalp pruritus. Although no statistically significant difference on the incidence of atopic disease among three groups has been found, serum IgE level in diffuse AA was higher than that in healthy controls, but was comparable to that in patchy AA group. Histopathology of lesional scalp biopsies showed more intense infiltration comprising of mononuclear cells, eosinophils, CD3 + , and CD8 + T cells around hair bulbs in diffuse AA group than in patchy AA group. Moreover, IgE level in diffuse AA patients positively correlated with intensity of infiltration by mononuclear cells, eosinophils, and CD8 + T cells. Conclusions: Hypersensitivity may be involved in pathogenesis of diffuse AA. The acute onset of diffuse AA may be related to intense local inflammatory infiltration of hair loss region and an increase in serum IgE level.

Canine Oral Eosinophilic Granuloma Treated with Electrochemotherapy

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Matías Nicolás Tellado

2014-01-01

Full Text Available A case of a canine oral eosinophilic granuloma in a 14-year-old female crossbred is described. The dog was presented with a history of ptyalism, halitosis, local pain, decreased appetite, and blood staining noted on food and water bowls. Clinical, hematologic, and biochemical examinations, abdominal ultrasonography, and 3-view chest radiographs were performed, and no metastases were found. Histopathologic examination of two 6 mm punch biopsies from the oral lesion revealed the presence of eosinophilic granulomatous lesions in the submucosa. After treatment with corticosteroids and wide spectrum antibiotics no significant changes in clinical signs and lesion size were observed. Electrochemotherapy (ECT, a novel tumor treatment routinely used for cutaneous and subcutaneous tumors in human patients in the European Union since 2006, was used to treat the eosinophilic granuloma. The procedure was performed under general anesthesia, followed by intravenous administration of bleomycin. Six weeks after treatment a complete response with disappearance of the mass and improvement of clinical signs were observed.

Eosinophil count, allergies, and rejection in pediatric heart transplant recipients.

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Arbon, Kate S; Albers, Erin; Kemna, Mariska; Law, Sabrina; Law, Yuk

2015-08-01

Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Evidence for a role of eosinophils in blister formation in bullous pemphigoid.

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de Graauw, E; Sitaru, C; Horn, M; Borradori, L; Yousefi, S; Simon, H-U; Simon, D

2017-07-01

Bullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear. To investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal-epidermal separation (DES). In an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium, DNase or blocking F(ab') 2 fragments to CD16, CD18, CD32 and CD64. Dermal-epidermal separation was assessed by light microscopy studies and quantified using Fiji software. Following activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal-epidermal junction of ex vivo skin. Dermal-epidermal separation was significantly reduced by blocking any of the following: Fcγ receptor binding (P = 0.048), eosinophil adhesion (P = 0.046), reactive oxygen species (ROS) production (P = 0.002), degranulation (P eosinophil extracellular trap (EET) formation (P = 0.048). Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. Dermal-epidermal separation by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of Eosinophilic Fasciitis during Infliximab Therapy for Psoriatic Arthritis

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Richard Hariman

2016-01-01

Full Text Available Eosinophilic fasciitis (EF is a rare disorder involving chronic inflammation of the fascia and connective tissue surrounding muscles, nerves, and blood vessels. While its pathogenesis is not entirely understood, this disorder is thought to be autoimmune or allergic in nature. We present here a case of a 59-year-old male who developed peripheral eosinophilia and subsequent eosinophilic fasciitis during treatment with infliximab. To our knowledge, eosinophilic fasciitis has not been previously described in patients during treatment with an inhibitor of tumor necrosis factor α.

The Role of Proton Pump Inhibitors in the Management of Pediatric Eosinophilic Esophagitis

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Carolina Gutiérrez-Junquera

2018-05-01

Full Text Available Eosinophilic esophagitis (EoE is a chronic, local, immune-mediated disorder characterized by symptoms of esophageal dysfunction and the presence of a dense eosinophilic infiltrate in the esophageal mucosa. Consensus diagnostic recommendations for EoE diagnosis included absence of histological response to a proton-pump inhibitor (PPI trial, to exclude gastro-oesophageal reflux disease (GERD-associated esophagitis. This recommendation exposed an entity known as “proton pump inhibitor-responsive esophageal eosinophilia” (PPI-REE, which refers to patients with EoE phenotype who are PPI-responsive and do not present GERD. In recent years, there is evidence which indicates that PPI-REE is a sub-phenotype of EoE with similar clinical, endoscopic, histological and genetic characteristics, as well as Th2-related inflammatory response. As a result, PPIs should be considered another treatment for EoE and not a diagnostic tool. PPI-REE was originally described in a case series which included two children and in two retrospective pediatric series. Later, a prospective pediatric study showed a high rate of response to PPIs at high doses with long-term maintenance at lower doses. PPI monotherapy in children with esophageal eosinophilia (EE has been observed to reduce eotaxin-3 expression in epithelial cells and to practically reverse the allergy and inflammatory transcriptome. These data reveal that PPIs are also an effective treatment for EoE in pediatric patients, although more studies are necessary in order to define the best induction and maintenance treatment regimen, the long-term safety profile and their influence on the occurrence of fibrosis and esophageal remodeling.

MR findings of eosinophilic granuloma

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Choi, Jong O; Yee, Mi Kyeung; Cho, Kil Ho [Yeungnam Univ. College of Medicine, Kyongsan (Korea, Republic of); Lee, Sung Moon [Keimyung Univ. College of Medicine, Taegu (Korea, Republic of); Lee, Young Hwan [Hyosung Catholic Univ. College of Medicine, Taegu (Korea, Republic of); Suh, Kyung Jin [Suhjoo MR Clinic, Taegu (Korea, Republic of)

1999-06-01

To describe the MR findings for the three phases of eosinophilic granuloma, as defined by Mirra's conventional radiographic criteria. Eighteen lesions in 14 patients with proven eosinophilic granuloma were retrospectively analyzed. Among this total, three vertebral lesions were excluded, and the remaining is were classified as early, middle, or late phase on the basis of Mirra's radiographic criteria. For each phase, we compared MR findings with regard to signal intensity, homogeneity, contrast enhancement, perilesional marrow edema, and soft tissue change. For the three vertebral lesions excluded because the application of radiographic criteria was difficult, MR findings for paravertebral soft tissue reaction and degree of cord compression were compared. Of the fifteen cases classified, eight were early phase, five were mid phase, and two were late phase. During each phase, all lesions except one, as seen on T1-weighted images(T1WI), showed iso-signal intensity. On T2WI, all lesions showed high signal intensity. Contrast study demonstrated marked contrast enhancement. Thus, no remarkable differences were found in the signal intensity degree of contrast enhancement of each phase. With regard to heterogeneity, this was demonstrated in most early phase lesions, reflecting necrosis and hemorrhage of those lesions. Soft tissue swelling was more severe during the early phase than the mid or late phase, but marrow edema was similar in each of the three phase. One of three patients with vertebraplana showed para-vertebral soft tissue swelling and cord compression, but this was not seen in the two other cases. For evalvating the extent of eosinophilic granuloma and its relationship with surrounding structures, MRI was superior to conventional radiography. During the early phase of the disease, lesions showed greater inhomogeneity and more aggressive soft tissue reaction than during the mid and late phase.The use of MRI for the evalvation of eosinophilic granuloma

Eosinophilic Esophagitis: Symptoms and Causes

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... to GERD medication Failure to thrive (poor growth, malnutrition and weight loss) When to see a doctor ... Originally, eosinophilic esophagitis was thought to be a childhood disease, but now it is known to be ...

Eosinophilic Esophagitis: Diagnosis and Treatment

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... as fatty or fried foods, tomato sauce, alcohol, chocolate, mint, garlic, onion, and caffeine, may make heartburn ... the waist up. Alternative medicine No alternative medicine therapies have been proved to treat eosinophilic esophagitis. Still, ...

Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus.

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Samarasinghe, Amali E; Melo, Rossana C N; Duan, Susu; LeMessurier, Kim S; Liedmann, Swantje; Surman, Sherri L; Lee, James J; Hurwitz, Julia L; Thomas, Paul G; McCullers, Jonathan A

2017-04-15

Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus-infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8 + T cell numbers in the airways. In vitro assays with primary or bone marrow-derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide-exposed eosinophils induced CD8 + T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity. Copyright © 2017 by The American Association of Immunologists, Inc.

Assessment of Schistosoma mansoni induced intestinal inflammation by means of eosinophil cationic protein, eosinophil protein X and myeloperoxidase before and after treatment with praziquantel

DEFF Research Database (Denmark)

Reimert, Claus Michael; Tukahebwa, Edridah M.; Kabatereine, Narcis B.

2008-01-01

Faecal concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX) and myeloperoxidase (MPO) were measured in extracts of stool samples obtained from a cohort of people (n=182) living in Bugoigo, a fishing community on the Eastern shore of Lake Albert, Buliisa District, in North...

Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo

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Chu, Derek K.; Jimenez-Saiz, Rodrigo; Verschoor, Christopher P.; Walker, Tina D.; Goncharova, Susanna; Llop-Guevara, Alba; Shen, Pamela; Gordon, Melissa E.; Barra, Nicole G.; Bassett, Jennifer D.; Kong, Joshua; Fattouh, Ramzi; McCoy, Kathy D.; Bowdish, Dawn M.; Erjefält, Jonas S.; Pabst, Oliver; Humbles, Alison A.; Kolbeck, Roland; Waserman, Susan

2014-01-01

Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4+/+ or il4−/− eosinophils. Eosinophils controlled CD103+ dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity. PMID:25071163

Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders.

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Barnig, Cindy; Alsaleh, Ghada; Jung, Nicolas; Dembélé, Doulaye; Paul, Nicodème; Poirot, Anh; Uring-Lambert, Béatrice; Georgel, Philippe; de Blay, Fréderic; Bahram, Seiamak

2015-01-01

Eosinophils are leukocytes that are released into the peripheral blood in a phenotypically mature state and are capable of being recruited into tissues in response to appropriate stimuli. Eosinophils, traditionally considered cytotoxic effector cells, are leukocytes recruited into the airways of asthma patients where they are believed to contribute to the development of many features of the disease. This perception, however, has been challenged by recent findings suggesting that eosinophils have also immunomodulatory functions and may be involved in tissue homeostasis and wound healing. Here we describe a transcriptome-based approach-in a limited number of patients and controls-to investigate the activation state of circulating human eosinophils isolated by flow cytometry. We provide an overview of the global expression pattern in eosinophils in various relevant conditions, e.g., eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Compared to healthy subjects, circulating eosinophils isolated from asthma patients differed in their gene expression profile which is marked by downregulation of transcripts involved in antigen presentation, pathogen recognition and mucosal innate immunity, whereas up-regulated genes were involved in response to non-specific stimulation, wounding and maintenance of homeostasis. Eosinophils from other hypereosinophilic disorders displayed a very similar transcriptional profile. Taken together, these observations seem to indicate that eosinophils exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis and suggest new roles for these cells in asthma immunobiology.

The imaging diagnosis of costal solitary eosinophilic granuloma

International Nuclear Information System (INIS)

Cui Fa; Feng Shiting

2007-01-01

Objective: To study the imaging features of costal eosinophilic granuloma so as to improve diagnosis accuracy of the disease. Methods: The clinical and imaging materials of 6 patients with costal solitary eosinophilic granuloma which were proved by surgery or histopathology were analyzed retrospectively. X-ray plain films were performed in all the cases, CT in 3 cases, 2 cases were received CT plain scan and I case received both CT plain scan and enhanced CT scan. Results: 4 cases of them located in the anterior ribs. All the lesions were round-like and 5 were single cavity and 1 was multiple cavities. 3 of them were expansile destruction and 3 were cystic destruction. Soft tissue mass around the lesion was identified. Conclusion: X-ray plain films integrating CT play an important role in diagnosis and differential diagnosis of the costal eosinophilic granuloma. (authors)

Diffuse eosinophilic gastroenteritis with antral obstruction: a case report

International Nuclear Information System (INIS)

Moon, Sung Hee; Kim, Young Bok; Lee, Koung Hee

2000-01-01

Eosinophilic gastroenteritis is a rare disease characterized by tissue eosinophilia that can involve different layers of the gut wall and cause various gastrointestinal symptoms. We describe the UGI and CT findings of a case of diffuse eosinophilic gastroenteritis with tumor-like antral obstruction due to thickening of the submucosa and muscle layer in a 21-year-old male. (author)

Diffuse eosinophilic gastroenteritis with antral obstruction: a case report

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Moon, Sung Hee; Kim, Young Bok; Lee, Koung Hee [National Police Hospital, Seoul (Korea, Republic of)

2000-02-01

Eosinophilic gastroenteritis is a rare disease characterized by tissue eosinophilia that can involve different layers of the gut wall and cause various gastrointestinal symptoms. We describe the UGI and CT findings of a case of diffuse eosinophilic gastroenteritis with tumor-like antral obstruction due to thickening of the submucosa and muscle layer in a 21-year-old male. (author)

Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells.

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Xi Zhang

Full Text Available Patients who have esophageal eosinophilia without gastroesophageal reflux disease (GERD nevertheless can respond to proton pump inhibitors (PPIs, which can have anti-inflammatory actions independent of effects on gastric acid secretion. In esophageal cell cultures, omeprazole has been reported to inhibit Th2 cytokine-stimulated expression of eotaxin-3, an eosinophil chemoattractant contributing to esophageal eosinophilia in eosinophilic esophagitis (EoE. The objective of this study was to elucidate molecular mechanisms underlying PPI inhibition of IL-4-stimulated eotaxin-3 production by esophageal cells.Telomerase-immortalized and primary cultures of esophageal squamous cells from EoE patients were treated with IL-4 in the presence or absence of acid-activated omeprazole or lansoprazole. We measured eotaxin-3 protein secretion by ELISA, mRNA expression by PCR, STAT6 phosphorylation and nuclear translocation by Western blotting, eotaxin-3 promoter activation by an exogenous reporter construct, and STAT6, RNA polymerase II, and trimethylated H3K4 binding to the endogenous eotaxin-3 promoter by ChIP assay. Omeprazole in concentrations ≥5 µM significantly decreased IL-4-stimulated eotaxin-3 protein secretion and mRNA expression. Lansoprazole also blocked eotaxin-3 protein secretion. Omeprazole had no effect on eotaxin-3 mRNA stability or on STAT6 phosphorylation and STAT6 nuclear translocation. Rather, omeprazole blocked binding of IL-4-stimulated STAT6, RNA polymerase II, and trimethylated H3K4 to the eotaxin-3 promoter.PPIs, in concentrations achieved in blood with conventional dosing, significantly inhibit IL-4-stimulated eotaxin-3 expression in EoE esophageal cells and block STAT6 binding to the promoter. These findings elucidate molecular mechanisms whereby patients with Th2 cytokine-driven esophageal eosinophilia can respond to PPIs, independent of effects on gastric acid secretion.

Bronchoalveolar lavage and technetium-99m glucoheptonate imaging in chronic eosinophilic pneumonia

International Nuclear Information System (INIS)

Lieske, T.R.; Sunderrajan, E.V.; Passamonte, P.M.

1984-01-01

A patient with chronic eosinophilic pneumonia was evaluated using bronchoalveolar lavage, technetium-99m glucoheptonate, and transbronchial lung biopsy. Bronchoalveolar lavage revealed 43 percent eosinophils and correlated well with results of transbronchial lung biopsy. Technetium-99m glucoheptonate lung imaging demonstrated intense parenchymal uptake. After eight weeks of corticosteroid therapy, the bronchoalveolar lavage eosinophil population and the technetium-99m glucoheptonate uptake had returned to normal. We suggest that bronchoalveolar lavage, with transbronchial lung biopsy, is a less invasive way than open lung biopsy to diagnose chronic eosinophilic pneumonia. The mechanism of uptake of technetium-99m glucoheptonate in this disorder remains to be defined

Work in progress: radionuclide imaging of indium-111-labeled eosinophils in mice

International Nuclear Information System (INIS)

Runge, V.M.; Rand, T.H.; Clanton, J.A.; Jones, J.P.; Colley, D.G.; Partain, C.L.; James, A.E. Jr.

1983-01-01

Eosinophils isolated from peritoneal exudates were labeled with indium-111-oxine and injected intravenously into sensitized mice. They became localized at sites of inflammation produced by intradermal injections of schistosomal antigen or Toxocara canis larvae, whereas labeled neutrophils did not. Intense uptake of eosinophils by normal spleen, liver, and bone marrow was noted, with tracer distribution effectively complete by 5 hours after injection. Indium-111-eosinophil studies appear to be quite sensitive to parasitic inflammatory reactions; in contrast, nonspecific inflammation such as that induced by turpentine causes localization of eosinophils, but to a lesser extent. This technique may be useful in the study of parasitic and allergic disease

Eosinophilic meningitis: a case series and review of literature of Angiostrongylus cantonensis and Gnathostoma spinigerum.

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Shah, I; Barot, S; Madvariya, M

2015-01-01

Eosinophilic meningitis is defined as the presence of >10 eosinophils/μL in cerebrospinal fluid (CSF) or at least 10% eosinophils in the total CSF leukocyte count. Eosinophilic meningitis has been reported in two case series and two case reports in India till date and has not been reported in children below 15 years of age. We present two children with eosinophilic meningitis with peripheral eosinophilia and the proposed etiologic agents based on the clinical setting and their response to antihelminthic agents.

Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice.

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Jacobsen, E A; Doyle, A D; Colbert, D C; Zellner, K R; Protheroe, C A; LeSuer, W E; Lee, N A; Lee, J J

2015-09-01

Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Wild-type or cytokine-deficient (IL-13(-/-) or IL-4(-/-) ) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4(+) T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4(+) T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role. The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eosinophilic fasciitis after parasite infection

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Marta Oliveira

2016-03-01

Full Text Available Eosinophilic fasciitis is a systemic inflammatory disease characterized by symmetrical swelling and skin induration of the distal portions of the arms and/or legs, evolving into a scleroderma-like appearance, accompanied by peripheral blood eosinophilia. It is a rare disease with a poorly understood etiology. Corticosteroid treatment remains the standard therapy, either taken alone or in association with an immunosuppressive drug. This paper presents a case of a male patient with palpebral edema and marked eosinophilia, diagnosed with intestinal parasitic infection in October 2006. He was treated with an antiparasitic drug, but both the swelling and the analytical changes remained. This was followed by a skin and muscle biopsy, which turned out to be compatible with eosinophilic fasciitis. There was progressive worsening of the clinical state, with stiffness of the abdominal wall and elevated inflammatory parameters, and the patient was referred to the Immunology Department, medicated with corticosteroids and methotrexate. Over the years there were therapeutic adjustments and other causes were excluded. Currently the patient continues to be monitored, and there is no evidence of active disease. The case described in this article is interesting because of the diagnosis of eosinophilic fasciitis probably associated/coexisting with a parasite infection. This case report differs from others in that there is an uncommon cause associated with the onset of the disease, instead of the common causes such as trauma, medication, non-parasitic infections or cancer.

TLR-Stimulated Eosinophils Mediate Recruitment and Activation of NK Cells In Vivo.

Science.gov (United States)

O'Flaherty, S M; Sutummaporn, K; Häggtoft, W L; Worrall, A P; Rizzo, M; Braniste, V; Höglund, P; Kadri, N; Chambers, B J

2017-06-01

Eosinophils like many myeloid innate immune cells can provide cytokines and chemokines for the activation of other immune cells upon TLR stimulation. When TLR-stimulated eosinophils were inoculated i.p. into wild-type mice, and NK cells were rapidly recruited and exhibited antitumour cytotoxicity. However, when mice depleted of CD11c + cells were used, a marked decrease in the number of recruited NK cells was observed. We postulated that CpG or LPS from the injected eosinophils could be transferred to host cells, which in turn could recruit NK cells. However, by inoculating mice deficient in TLR4 or TLR9 with LPS or CpG-stimulated eosinophils respectively, NK cell recruitment was still observed alongside cytotoxicity and IFNγ production. CpG stimulation of eosinophils produced the pro-inflammatory cytokine IL-12 and the chemokine CXCL10, which are important for NK cell activation and recruitment in vivo. To demonstrate the importance of CXCL10 in NK cell recruitment, we found that CpG-stimulated eosinophils pretreated with the gut microbial metabolite butyrate had reduced expression and production of CXCL10 and IL-12 and concomitantly were poor at recruitment of NK cells and inducing IFNγ in NK cells. Therefore, eosinophils like other innate immune cells of myeloid origin can conceivably stimulate NK cell activity. In addition, products of the gut microbiota can be potential inhibitors of NK cell. © 2017 The Foundation for the Scandinavian Journal of Immunology.

Synergic production of neutrophil chemotactic activity by colonic epithelial cells and eosinophils.

Science.gov (United States)

Dent, Gordon; Loweth, Sam C; Hasan, Anwar Matar; Leslie, Fiona M

2014-10-01

The presence of eosinophils in the lumen and mucosa of the intestine is characteristic of both ulcerative colitis (UC) and Crohn's disease (CD). There is evidence of eosinophil activation in the intestine during acute inflammatory episodes of these diseases; these episodes are also characterized by an influx of neutrophils, which have the potential to cause extensive tissue damage. We undertook a study to determine whether eosinophils in contact with colonic epithelial cells produce factors that may attract neutrophils in response to immunological stimulation. Neutrophil chemotactic activity (NCA) and concentrations of three neutrophil-attracting CXC chemokines - CXCL1 (Groα), CXCL5 (Ena78) and CXCL8 (IL8) - were measured in supernatants of T84 colonic epithelial cells and blood eosinophils or eosinophil-like myeloid leukaemia cells (AML14.3D10), alone or in combination. Cells were stimulated with serum-opsonized zymosan (OZ) particles. NCA (Peosinophil co-cultures were significantly higher than in the supernatants of either cell type alone. Release of CXCL1 (Peosinophils but not higher than from OZ-stimulated epithelial cells. Eosinophils and colonic epithelial cells exhibit synergy in production of neutrophil chemoattractants in response to immunological stimulation. This may represent a mechanism for exaggerated recruitment of neutrophils to the intestine in response to acute infection in conditions that are characterized by the presence of eosinophils in the bowel. Copyright © 2014 Elsevier GmbH. All rights reserved.

Functional and phenotypic evaluation of eosinophils from patients with the acute form of paracoccidioidomycosis.

Science.gov (United States)

Braga, Fernanda Gambogi; Ruas, Luciana Pereira; Pereira, Ricardo Mendes; Lima, Xinaida Taligare; Antunes, Edson; Mamoni, Ronei Luciano; Blotta, Maria Heloisa Souza Lima

2017-05-01

Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment. However, the role of eosinophils in PCM has never been evaluated. This study aimed to assess the phenotypic and functional characteristics of eosinophils in PCM. In 15 patients with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES) and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were higher levels of chemokines and granule proteins in the peripheral blood of patients compared to controls. Isolation of eosinophils from blood revealed a higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls, and a lower population of CD80+ cells. We also evaluated the fungicidal capacity of eosinophils in vitro. Our results revealed that eosinophils from PCM patients and controls exhibit similar ability to kill P. brasiliensis yeast cells, although eosinophils of patients were less responsive to IL-5 stimulation than controls. In conclusion, we suggest that eosinophils might play a role in the host response to fungi and in the pathophysiology of PCM by inducing an intense and systemic inflammatory response in the initial phase of the infection.

Increased CD69 Expression on Peripheral Eosinophils from Patients with Food Protein-Induced Enterocolitis Syndrome.

Science.gov (United States)

Wada, Taizo; Matsuda, Yusuke; Toma, Tomoko; Koizumi, Eiko; Okamoto, Hiroyuki; Yachie, Akihiro

2016-01-01

Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE-mediated food allergy. We recently described a significant increase in fecal eosinophil-derived neurotoxin (EDN) after ingestion of the causative food. However, little is known about the activation status of circulating eosinophils in patients with an acute FPIES reaction. Surface CD69 expression was assessed by flow cytometry on peripheral eosinophils from 5 patients with FPIES before and after ingestion of the causative food. Fecal EDN was measured by enzyme-linked immunosorbent assay. No eosinophil activation was observed before ingestion; however, a significant increase in CD69 expression on eosinophils after an acute FIPES reaction was demonstrated in all of the patients. There was no significant change in absolute eosinophil counts in the peripheral blood. The levels of fecal EDN increased on the day after ingestion of the causative food in all patients. These results suggest that circulating eosinophils as well as eosinophils in the intestinal mucosal tissue are activated in acute FPIES reactions and might be associated with systemic immune events in FPIES. © 2016 S. Karger AG, Basel.

MR findings of calvarial eosinophilic granuloma

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Choi, Gi Bok; Son, Seok Hyun; Eun, Choong Ki; Park, Sung Kun; Han, Sang Suk [Pusan Paik Hospital, Inje Univ., Pusan (Korea, Republic of); Choi, Sun Seob [Donga Univ. College of Medicine, Pusan (Korea, Republic of); Kim, Seong Min [Kosin Univ. College of Medicine, Pusan (Korea, Republic of); Kim, Chang Soo [Maryknoll Hospital, Pusan (Korea, Republic of)

2001-03-01

The purpose of this study was to evaluate the MR findings of calvarial eosinophilic granuloma. We reviewed the MR imaging studies of nine patients [M:F=3:6, aged 6-35 (mean, 20.5) years] with pathologically proven eosinophilic granuloma in the calvaria. The findings were evaluated for involvement of the diploic space, changes in adjacent bone marrow, distinction of the transitional zone, pattern of bone destruction, signal intensity and contrast enhancement of the tumor, and contrast enhancement of the adjacent dura. All lesions involved the diploic space, showed no change in adjacent bone marrow, and had a distinct transitional zone. In most (8/9) cases there was asymmetric bony destruction. On T1-weighted images, signal intensities of the tumors varied, while on T2-weighted images, hyperintensity was observed in seven cases, isointensity in one, and hypointensity in one. After the administration of contrast material, enhancement was homogeneous in four cases and inhomogeneous in five. Enhancement of the adjacent dura was demonstrated in all nine cases. The characteristic MR findings of calvarial eosinophilic granuloma are variable signal intensity on T1WI, high signal intensity on T2WI, and marked contrast enhancement; in addition, there is a distinct transitional zone, asymmetrical bony destruction, and associated dural enhancement.

A pilot study of omalizumab in eosinophilic esophagitis.

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Denise Loizou

Full Text Available Eosinophilic disorders of the gastrointestinal tract are an emerging subset of immune pathologies within the spectrum of allergic inflammation. Eosinophilic Esophagitis (EoE, once considered a rare disease, is increasing in incidence, with a rate of over 1 in 10,000 in the US, for unknown reasons. The clinical management of EoE is challenging, thus there is an urgent need for understanding the etiology and pathophysiology of this eosinophilic disease to develop better therapeutic approaches. In this open label, single arm, unblinded study, we evaluated the effects of an anti-IgE treatment, omalizumab, on local inflammation in the esophagus and clinical correlates in patients with EoE. Omalizumab was administered for 12 weeks to 15 subjects with long standing EoE. There were no serious side effects from the treatment. Esophageal tissue inflammation was assessed both before and after therapy. After 3 months on omalizumab, although tissue Immunoglobulin E (IgE levels were significantly reduced in all but two of the subjects, we found that full remission of EoE, which is defined as histologic and clinical improvement only in 33% of the patients. The decrease in tryptase-positive cells and eosinophils correlated significantly with the clinical outcome as measured by improvement in endoscopy and symptom scores, respectively. Omalizumab-induced remission of EoE was limited to subjects with low peripheral blood absolute eosinophil counts. These findings demonstrate that in a subset of EoE patients, IgE plays a role in the pathophysiology of the disease and that anti-IgE therapy with omalizumab may result in disease remission. Since this study is open label there is the potential for bias, hence the need for a larger double blind placebo controlled study. The data presented in this pilot study provides a foundation for proper patient selection to maximize clinical efficacy.

Expression and subcellular localization of the Qa-SNARE syntaxin17 in human eosinophils

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Carmo, Lívia A.S.; Dias, Felipe F.; Malta, Kássia K.; Amaral, Kátia B.; Shamri, Revital; Weller, Peter F.; Melo, Rossana C.N.

2015-01-01

Background: SNARE members mediate membrane fusion during intracellular trafficking underlying innate and adaptive immune responses by different cells. However, little is known about the expression and function of these proteins in human eosinophils, cells involved in allergic, inflammatory and immunoregulatory responses. Here, we investigate the expression and distribution of the Qa-SNARE syntaxin17 (STX17) within human eosinophils isolated from the peripheral blood. Methods: Flow cytometry and a pre-embedding immunonanogold electron microscopy (EM) technique that combines optimal epitope preservation and secondary Fab-fragments of antibodies linked to 1.4 nm gold particles for optimal access to microdomains, were used to investigate STX17. Results: STX17 was detected within unstimulated eosinophils. Immunogold EM revealed STX17 on secretory granules and on granule-derived vesiculotubular transport carriers (Eosinophil Sombrero Vesicles-EoSVs). Quantitative EM analyses showed that 77.7% of the granules were positive for STX17 with a mean±SEM of 3.9±0.2 gold particles/granule. Labeling was present on both granule outer membranes and matrices while EoSVs showed clear membrane-associated labeling. STX17 was also present in secretory granules in eosinophils stimulated with the cytokine tumor necrosis factor alpha (TNF-α) or the CC-chemokine ligand 11 CCL11 (eotaxin-1), stimuli that induce eosinophil degranulation. The number of secretory granules labeled for STX17 was significantly higher in CCL11 compared with the unstimulated group. The level of cell labeling did not change when unstimulated cells were compared with TNF-α-stimulated eosinophils. Conclusions: The present study clearly shows by immunanonogold EM that STX17 is localized in eosinophil secretory granules and transport vesicles and might be involved in the transport of granule-derived cargos. - Highlights: • First demonstration of the Qa-SNARE syntaxin-17 (STX17) in human eosinophils. • High

Expression and subcellular localization of the Qa-SNARE syntaxin17 in human eosinophils

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Carmo, Lívia A.S.; Dias, Felipe F.; Malta, Kássia K.; Amaral, Kátia B. [Laboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora, UFJF, Juiz de Fora, MG (Brazil); Shamri, Revital; Weller, Peter F. [Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States); Melo, Rossana C.N., E-mail: rossana.melo@ufjf.edu.br [Laboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora, UFJF, Juiz de Fora, MG (Brazil); Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States)

2015-10-01

Background: SNARE members mediate membrane fusion during intracellular trafficking underlying innate and adaptive immune responses by different cells. However, little is known about the expression and function of these proteins in human eosinophils, cells involved in allergic, inflammatory and immunoregulatory responses. Here, we investigate the expression and distribution of the Qa-SNARE syntaxin17 (STX17) within human eosinophils isolated from the peripheral blood. Methods: Flow cytometry and a pre-embedding immunonanogold electron microscopy (EM) technique that combines optimal epitope preservation and secondary Fab-fragments of antibodies linked to 1.4 nm gold particles for optimal access to microdomains, were used to investigate STX17. Results: STX17 was detected within unstimulated eosinophils. Immunogold EM revealed STX17 on secretory granules and on granule-derived vesiculotubular transport carriers (Eosinophil Sombrero Vesicles-EoSVs). Quantitative EM analyses showed that 77.7% of the granules were positive for STX17 with a mean±SEM of 3.9±0.2 gold particles/granule. Labeling was present on both granule outer membranes and matrices while EoSVs showed clear membrane-associated labeling. STX17 was also present in secretory granules in eosinophils stimulated with the cytokine tumor necrosis factor alpha (TNF-α) or the CC-chemokine ligand 11 CCL11 (eotaxin-1), stimuli that induce eosinophil degranulation. The number of secretory granules labeled for STX17 was significantly higher in CCL11 compared with the unstimulated group. The level of cell labeling did not change when unstimulated cells were compared with TNF-α-stimulated eosinophils. Conclusions: The present study clearly shows by immunanonogold EM that STX17 is localized in eosinophil secretory granules and transport vesicles and might be involved in the transport of granule-derived cargos. - Highlights: • First demonstration of the Qa-SNARE syntaxin-17 (STX17) in human eosinophils. • High

Participation of CD11b and F4/80 molecules in the conjunctival eosinophilia of experimental allergic conjunctivitis.

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Fukushima, Atsuki; Ishida, Waka; Ojima, Ayako; Kajisako, Mina; Sumi, Tamaki; Yamada, Jun; Tsuru, Emi; Miyazaki, Jun-ichi; Tominaga, Akira; Yagita, Hideo

2010-01-01

CD11b and F4/80 are macrophage surface markers. How these molecules participate in allergic eosinophil infiltration remains unclear. We examined the roles CD11b and F4/80 play in the conjunctival eosinophil infiltration associated with experimental allergic conjunctivitis. Ragweed-immunized BALB/c mice were challenged with ragweed in eye drops to induce conjunctival eosinophil infiltration. The effect of challenge on conjunctival CD11b+ and F4/80+ cell numbers was determined by immunohistochemistry. In the same model, blocking anti-CD11b and anti-F4/80 Abs were injected intraperitoneally during the induction or the effector phase, or subconjunctivally 2 h before challenge, to determine their effect on challenge-induced conjunctival eosinophilia. To examine whether eosinophils express CD11b and F4/80 molecules, splenocytes from IL-5 gene-electroporated mice were subjected to flow cytometric analysis. To clarify the involvement of CD11b and F4/80 in conjunctival eosinophil infiltration, mice were intraperitoneally injected with anti-CD11b and anti-F4/80 Abs and then subconjunctivally injected with eotaxin to induce conjunctival eosinophilia. Ragweed challenge elevated conjunctival CD11b+ and F4/80+ cell numbers. Systemic anti-CD11b and anti-F4/80 Ab treatments during the effector phase, but not in either the induction phase or the local injection of Ab, suppressed conjunctival eosinophil infiltration in ragweed-induced conjunctivitis. Most splenic eosinophils from IL-5 gene-introduced mice expressed CD11b and F4/80. Systemic anti-CD11b and anti-F4/80 Ab treatment suppressed conjunctival eosinophilia induced by subconjunctival eotaxin injection. CD11b and F4/80 appear to participate in conjunctival eosinophil infiltration in allergic conjunctivitis. Their involvement in conjunctival eosinophilia appears to be due to their expression on eosinophils rather than on macrophages. 2009 S. Karger AG, Basel.

MHC Class II and CD9 in Human Eosinophils Localize to Detergent-Resistant Membrane Microdomains

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Akuthota, Praveen; Melo, Rossana C. N.; Spencer, Lisa A.

2012-01-01

Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor–stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR–containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4+ T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils. PMID:21885678

MHC Class II and CD9 in human eosinophils localize to detergent-resistant membrane microdomains.

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Akuthota, Praveen; Melo, Rossana C N; Spencer, Lisa A; Weller, Peter F

2012-02-01

Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor-stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR-containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4(+) T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils.

Titanium dioxide nanoparticles induce human eosinophil adhesion onto endothelial EA.hy926 cells via activation of phosphoinositide 3-kinase/Akt cell signalling pathway.

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Murphy-Marion, Maxime; Girard, Denis

2018-02-01

The use of nanoparticles (NPs) for developing new therapeutic strategies in a variety of diseases is gaining increasing attention. However, NPs could possess undesired effects, including pro-inflammatory activities. Despite the fact that several studies reported that NPs may induce or exacerbate eosinophilic inflammation in vivo in rodents, the information regarding the direct interaction between NPs and human eosinophils is lacking. In the present study, we test the possibility that NPs could alter the capacity of human eosinophils to adhere onto a cellular substratum. Using a panel of NPs, we found that several were able to increase the adhesion of human eosinophil onto endothelial EA.hy926 cells. Among them, TiO 2 NPs were the most potent and we therefore pursue this study with these NPs. TiO 2 NPs were found to increase the adhesion of eosinophils in a concentration dependent fashion. TiO 2 NPs did not alter the cell surface expression of a panel of cellular adhesion molecules, but CD29. Indeed, a weak to moderate, but significant, decrease of CD29 was observed after 30min but returned to normal levels after 90min. TiO 2 NPs were found to activate Akt, one important target of phosphoinositide 3-kinase (PI3K). However, despite the fact that cells were fully responsive to the cytokine GM-CSF activating both Akt and Erk-1/2, TiO 2 NPs did not activate Erk-1/2. Using a pharmacological approach with the PI3K/Akt inhibitor, wortmannin, the ability of TiO 2 NPs to activate Akt was drastically inhibited and, further, their capacity to increase adhesion of eosinophils was reversed. This study provides insights into the effects of NPs on the biology of human eosinophils indicating that as other agents, NPs, namely TiO 2 NPs, can induce intracellular events associated with a cellular function, adhesion. Copyright © 2017 Elsevier GmbH. All rights reserved.

Protective Role of Eosinophils and TNFa after Ozone Inhalation.

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Fryer, Allison D; Jacoby, David B; Wicher, Sarah A

2017-03-01

Exposure to ozone induces deleterious responses in the airways that include shortness of breath, inflammation, and bronchoconstriction. People with asthma have increased airway sensitivity to ozone and other irritants. Dr. Allison Fryer and colleagues addressed how exposure to ozone affects the immune and physiological responses in guinea pigs. Guinea pigs are considered a useful animal model for studies of respiratory and physiological responses in humans; their response to airborne allergens is similar to that in humans and shares some features of allergic asthma. Fryer and colleagues had previously observed that within 24 hours of exposure, ozone not only induced bronchoconstriction but also stimulated the production of new cells in the bone marrow, where all white blood cells develop. As a result of ozone exposure, increased numbers of newly synthesized white blood cells, particularly eosinophils, moved into the blood and lungs. The central hypothesis of the current study was that newly synthesized eosinophils recruited to the lungs 3 days after ozone exposure were beneficial to the animals because they reduced ozoneinduced bronchoconstriction. The investigators also hypothesized that the beneficial effect seen in normal (nonsensitized) animals was lost in animals that had been injected with an allergen, ovalbumin (sensitized). They also planned to explore the effects of inhibitors of certain cytokines (cellsignaling molecules). Immune responses in sensitized animals are dominated by a Th2 pattern, which is characterized by the synthesis of cytokines (interleukin [IL]-4, IL-5, and IL-13) and the Th2 subset of CD4+ T lymphocytes and the cells they activate (predominantly eosinophils, and B lymphocytes that switch to making immunoglobulin E [IgE]). Thus, sensitized animals were used as a model of allergic humans, whose immune responses tend to be dominated by IgE. Fryer and colleagues exposed normal and sensitized (allergic) guinea pigs to 2 ppm ozone or filtered

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) presenting as diffuse myositis.

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Parent, Marc-Etienne; Larue, Sandrine; Ellezam, Benjamin

2014-11-21

Eosinophilic granulomatosis with polyangiitis is a complex multisystemic syndrome with heterogeneous presentation. Most often, there is a clinical history of asthma or other atopic conditions, and current presentation generally includes signs of cutaneous or pulmonary involvement. Very few reports described myalgia or weakness as the chief complaint. Of these, only a few included muscle biopsy evaluation and none showed convincing evidence of primary myositis. We believe this report is the first to demonstrate true myositis in the setting of early eosinophilic granulomatosis with polyangiitis. This report describes a 74 year old Caucasian man, with no known allergies, presenting severe myalgia, muscle weakness, jaw claudication, and fever. Blood work showed marked eosinophilia and high creatine kinase levels. Biceps brachialis muscle biopsy revealed eosinophilic necrotizing vasculitis and true myositis with myophagocytosis of non-necrotic fibers and strong sarcolemmal MHC-1 overexpression by immunohistochemistry. This patient was successfully treated with prednisone and azathioprine. Our finding of true myositis in a case of eosinophilic granulomatosis with polyangiitis suggests that primary auto-immunity against muscle fibers, distinct from the secondary effects of vasculitis, can occur in this entity and may represent an overlap syndrome. Early recognition of eosinophilic granulomatosis with polyangiitis in patients presenting with myositis may provide an opportunity to treat the vasculitis before onset of severe multisystemic disease. We recommend the use of muscle biopsy with immunohistochemistry for MHC-1 to confirm the diagnosis of myositis in the setting of eosinophilic granulomatosis with polyangiitis.

Differential Activation of Airway Eosinophils Induces IL-13 Mediated Allergic Th2 Pulmonary Responses in Mice

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Jacobsen, EA; Doyle, AD; Colbert, DC; Zellner, KR; Protheroe, CA; LeSuer, WE; Lee, NA.; Lee, JJ

2015-01-01

Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild type or cytokine deficient (IL-13−/− or IL-4−/−) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophildeficient mice, which induced no immune/inflammatory changes either in the lung or lung draining lymph nodes (LDLNs), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLNs. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4 and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13 whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. PMID:26009788

Mixed Herbal Medicine Induced Diffuse Infiltrative Lung Disease: The HRCT and Histopathologic Findings

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Kim, Tae Gyu; Shin, Eun A; Kim, Joung Sook

2010-01-01

The purpose of this study was to evaluate the high-resolution CT (HRCT) and pathologic findings of mixed herbal medicine-induced diffuse interstitial lung disease. Eight patients (6 women and 2 men, age range: 31 to 81 years, mean age: 51.4 years) who presented with cough or dyspnea after taking mixed herbal medicine were included in this study. All the patients underwent plain chest radiography and HRCT. We obtained pathologic specimens from 7 patients via fluoroscopy guided large bore cutting needle biopsy and transbronchial lung biopsy. All the patients were treated with steroid therapy. The most common HRCT finding was bilateral diffuse ground glass opacity (n=7), followed by peribronchial consolidation (n=5) and inter- or intralobular septal thickening (n=2). For the disease distribution, the lower lung zone was dominantly involved. The pathologic results of 7 patients were nonspecific interstitial pneumonia (n=3), bronchiolitis obliterans organizing pneumonia (n=2), hypersensitivity pneumonitis (n=1) and eosinophilic pneumonia (n=1). Irrespective of the pathologic results, all 8 patients improved clinically and radiologically after steroid treatment. The HRCT findings of mixed herbal medicine-induced diffuse infiltrative lung disease were mainly bilateral diffuse ground glass opacity, peribronchial consolidation and dominant involvement of the lower lung zone. Those pathologic findings were nonspecific and the differential diagnosis could include interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis and eosinophilic pneumonia

Mixed Herbal Medicine Induced Diffuse Infiltrative Lung Disease: The HRCT and Histopathologic Findings

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Kim, Tae Gyu; Shin, Eun A [Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Kim, Joung Sook [Mokdong Hospital, Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

2010-12-15

The purpose of this study was to evaluate the high-resolution CT (HRCT) and pathologic findings of mixed herbal medicine-induced diffuse interstitial lung disease. Eight patients (6 women and 2 men, age range: 31 to 81 years, mean age: 51.4 years) who presented with cough or dyspnea after taking mixed herbal medicine were included in this study. All the patients underwent plain chest radiography and HRCT. We obtained pathologic specimens from 7 patients via fluoroscopy guided large bore cutting needle biopsy and transbronchial lung biopsy. All the patients were treated with steroid therapy. The most common HRCT finding was bilateral diffuse ground glass opacity (n=7), followed by peribronchial consolidation (n=5) and inter- or intralobular septal thickening (n=2). For the disease distribution, the lower lung zone was dominantly involved. The pathologic results of 7 patients were nonspecific interstitial pneumonia (n=3), bronchiolitis obliterans organizing pneumonia (n=2), hypersensitivity pneumonitis (n=1) and eosinophilic pneumonia (n=1). Irrespective of the pathologic results, all 8 patients improved clinically and radiologically after steroid treatment. The HRCT findings of mixed herbal medicine-induced diffuse infiltrative lung disease were mainly bilateral diffuse ground glass opacity, peribronchial consolidation and dominant involvement of the lower lung zone. Those pathologic findings were nonspecific and the differential diagnosis could include interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis and eosinophilic pneumonia

Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal fibroblasts.

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Shin, Seung-Heon; Ye, Mi-Kyung; Choi, Sung-Yong; Kim, Yee-Hyuk

2016-06-01

Eosinophils and fibroblasts are known to play major roles in the pathogenesis of nasal polyps. Fungi are commonly found in nasal secretion and are associated with airway inflammation. To investigate whether activated eosinophils by airborne fungi can influence the production of extracellular matrix (ECM) from nasal fibroblasts. Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria or Aspergillus, respectively, for 24 hours and ECM messenger RNA (mRNA) and protein expressions were measured. Eosinophils isolated from healthy volunteers were stimulated with Alternaria or Aspergillus for 4 hours then superoxide, eosinophil peroxidase, and transforming growth factor β1 were measured. Then activated eosinophils were cocultured with nasal fibroblasts for 24 hours, and ECM mRNA expressions were measured. Alternaria strongly enhanced ECM mRNA expression and protein production from nasal fibroblasts. Alternaria also induced the production of superoxide, eosinophil peroxidase, and transforming growth factor β1 from eosinophils, and activated eosinophils enhanced ECM mRNA expression when they were cocultured without the Transwell insert system. Eosinophils activated with Alternaria enhanced ECM mRNA expression from nasal polyp fibroblasts. Alternaria plays an important role in tissue fibrosis in the pathogenesis of nasal polyps by directly or indirectly influencing the production of ECM from nasal fibroblasts. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease

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Uderhardt, Stefan; Ackermann, Jochen A.; Fillep, Tobias; Hammond, Victoria J.; Willeit, Johann; Stark, Konstantin; Rossaint, Jan; Schubert, Irene; Mielenz, Dirk; Dietel, Barbara; Raaz-Schrauder, Dorette; Ay, Cihan; Thaler, Johannes; Heim, Christian; Collins, Peter W.; Schabbauer, Gernot; Mackman, Nigel; Voehringer, David; Nadler, Jerry L.; Lee, James J.; Massberg, Steffen; Rauh, Manfred; O’Donnell, Valerie B.

2017-01-01

Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease. PMID:28566277

Echocardiographic Changes in Eosinophilic Endocarditis Induced by Churg-Strauss Syndrome.

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Masaki, Nobuyuki; Issiki, Ami; Kirimura, Masato; Kamiyama, Tetsuo; Sasaki, Osamu; Ito, Hiroyuki; Maruyama, Yoshiaki; Nishioka, Toshihiko

Eosinophilic myocarditis may be accompanied by Churg-Strauss syndrome (CSS). We report a case of CSS that was accompanied by myocardial changes in the early stage. A 71-year-old woman complained of mild chest pain at rest, but routine echocardiography did not reveal any endocardial abnormalities. Four months later, the patient was hospitalized due to congestive heart failure with neuropathy of both upper extremities. A diagnosis of eosinophilic myocarditis was made based on the patient's laboratory results and the presence of mural thrombus. This case illustrates that, although early eosinophilic myocarditis is an important differential diagnosis in patients with chest pain, it may be difficult to identify in without an apparent mural thrombus.

Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients.

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Wright, Adam; Mahaut-Smith, Martyn; Symon, Fiona; Sylvius, Nicolas; Ran, Shaun; Bafadhel, Mona; Muessel, Michelle; Bradding, Peter; Wardlaw, Andrew; Vial, Catherine

2016-06-15

Eosinophils play an important role in the pathogenesis of asthma and can be activated by extracellular nucleotides released following cell damage or inflammation. For example, increased ATP concentrations were reported in bronchoalveolar lavage fluids of asthmatic patients. Although eosinophils are known to express several subtypes of P2 receptors for extracellular nucleotides, their function and contribution to asthma remain unclear. In this article, we show that transcripts for P2X1, P2X4, and P2X5 receptors were expressed in healthy and asthmatic eosinophils. The P2X receptor agonist α,β-methylene ATP (α,β-meATP; 10 μM) evoked rapidly activating and desensitizing inward currents (peak 18 ± 3 pA/pF at -60 mV) in healthy eosinophils, typical of P2X1 homomeric receptors, which were abolished by the selective P2X1 antagonist NF449 (1 μM) (3 ± 2 pA/pF). α,β-meATP-evoked currents were smaller in eosinophils from asthmatic patients (8 ± 2 versus 27 ± 5 pA/pF for healthy) but were enhanced following treatment with a high concentration of the nucleotidase apyrase (17 ± 5 pA/pF for 10 IU/ml and 11 ± 3 pA/pF for 0.32 IU/ml), indicating that the channels are partially desensitized by extracellular nucleotides. α,β-meATP (10 μM) increased the expression of CD11b activated form in eosinophils from healthy, but not asthmatic, donors (143 ± 21% and 108 ± 11% of control response, respectively). Furthermore, α,β-meATP increased healthy (18 ± 2% compared with control 10 ± 1%) but not asthmatic (13 ± 1% versus 10 ± 0% for control) eosinophil adhesion. Healthy human eosinophils express functional P2X1 receptors whose activation leads to eosinophil αMβ2 integrin-dependent adhesion. P2X1 responses are constitutively reduced in asthmatic compared with healthy eosinophils, probably as the result of an increase in extracellular nucleotide concentration. Copyright © 2016 by The American Association of Immunologists, Inc.

Leukotriene Receptor Antagonists in the Treatment of Asthma: Implications for Eosinophilic Inflammation

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Redwan Moqbel

1999-01-01

Full Text Available Recent advances in the treatment and management of asthma have suggested that leukotriene (LT receptor antagonists may be very beneficial as a second generation therapy with steroid-sparing properties and negligible side effects. These agents have shown interesting effects on peripheral blood and sputum eosinophils. A major contributor to the damage in the airway of asthmatic patients is the eosinophil, which, upon activation, releases a battery of granule-associated cytotoxic, cationic proteins, including the major basic protein and eosinophil peroxidase, and membrane-derived de novo-synthesized bioactive lipid mediators, including LTC4, LTD4 and LTE4, as well as platelet activating factor. These products have deleterious effects on the airway tissue including mucosal and smooth muscle layers. Accumulating evidence suggests that these agents may also influence the accumulation and maintenance of eosinophilic responses at the site of inflammation. This article reviews the possible anti-inflammatory mode of action of these therapies. It also discusses where there may be a gap in the knowledge regarding the potential direct and indirect effects of LT modifiers on eosinophil function and recruitment.

Food and aeroallergens in eosinophilic esophagitis: role of the allergist in patient management.

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Aceves, Seema S

2014-07-01

Eosinophilic esophagitis is a clinicopathologic disease of increasing worldwide prevalence that is triggered by food antigens. The concurrent management of all of the atopic diseases affecting a single individual is likely to be important for successful long-term eosinophilic esophagitis management. This review covers the role of the allergist in eosinophilic esophagitis with a focus on the literature from the past 2  years. Studies in the past 2  years document that testing for immediate and delayed allergic hypersensitivity to foods can be of utility in building elimination diets in children, but that this may not be the case in adults. In addition, it has been shown that a number of cells and interleukins involved in Th2 inflammation such as invariant natural killer T cells, basophils, and interleukin-9 are important in eosinophilic esophagitis pathogenesis. Finally, the role of foods in generating esophageal remodeling has been shown using murine models. Recent studies support the role of the allergist in eosinophilic esophagitis management, especially for food allergen testing, interpretation, and the management of food allergies concurrent atopic diatheses. In addition, allergists have made significant research contributions in our understanding of eosinophilic esophagitis.

Human eosinophils - potential pharmacological model applied in human histamine H4 receptor research.

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Grosicki, Marek; Kieć-Kononowicz, Katarzyna

2015-01-01

Histamine and histamine receptors are well known for their immunomodulatory role in inflammation. In this review we describe the role of histamine and histamine H4 receptor on human eosinophils. In the first part of article we provide short summary of histamine and histamine receptors role in physiology and histamine related therapeutics used in clinics. We briefly describe the human histamine receptor H4 and its ligands, as well as human eosinophils. In the second part of the review we provide detailed description of known histamine effects on eosinophils including: intracellular calcium concentration flux, actin polymerization, cellular shape change, upregulation of adhesion proteins and cellular chemotaxis. We provide proofs that these effects are mainly connected with the activation of histamine H4 receptor. When examining experimental data we discuss the controversial results and limitations of the studies performed on isolated eosinophils. In conclusion we believe that studies on histamine H4 receptor on human eosinophils can provide interesting new biomarkers that can be used in clinical studies of histamine receptors, that in future might result in the development of new strategies in the treatment of chronic inflammatory conditions like asthma or allergy, in which eosinophils are involved.

Impaired esophageal motor function in eosinophilic esophagitis.

Science.gov (United States)

Santander, Cecilio; Chavarría-Herbozo, Carlos M; Becerro-González, Irene; Burgos-Santamaría, Diego

2015-10-01

Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.

Genetics of Eosinophilic Esophagitis

Science.gov (United States)

2012-03-01

disease of the esophagus that affects at least 4 in 10,000 persons.1 Although symptomatically resembling gastroe - sophageal reflux disease, EE is...clinically defined as esophageal eosinophilia (>_15 intraepithelial eosinophils per high-powered field) in the absence of abnormal acid reflux disease...that distinguish eosin- ophilic esophagitis (EoE) from other inflammatory disorders, including gastroesophageal reflux disease (GERD). As the prev

Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

DEFF Research Database (Denmark)

Gudbjartsson, Daniel F; Bjornsdottir, Unnur S; Halapi, Eva

2009-01-01

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts.......2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated...

X-ray and CT findings of costal eosinophilic granuloma

International Nuclear Information System (INIS)

Tu Zhanhai; Lin Zhengyu; Chen Yiguang

2010-01-01

Objective: To study the X-ray and CT features of costal eosinophilic granuloma for a better understanding. Methods: Eight patients with costal eosinophilic granuloma proved by surgery or biopsy were analyzed retrospectively. All patients had X-ray plain film, 6 patients had CT examination, including a case of enhanced CT scan. Results: All 8 lesions were solitary. Six lesions were in the anterior rib and 2 in the posterior rib. On X-ray, all case showed single cavity and oval lesion with clear boundary. On CT images, 5 lesions demonstrated expansile destruction of bone with cortical bone thinning, and 3 were osteolystic destruction with soft tissue mass around. On the patient with enhanced CT scan, the lesions showed a moderate and uniform enhancement. Conclusion: The X-ray and CT findings of costal eosinophilic granuloma are characteristic. (authors)

The environmental pollutant hexachlorobenzene causes eosinophilic and granulomatous inflammation and in vitro airways hyperreactivity in the Brown Norway rat

International Nuclear Information System (INIS)

Michielsen, C.; Zeamari, S.; Vos, J.; Leusink-Muis, A.; Bloksma, N.

2002-01-01

Based on observations that the persistent environmental pollutant hexachlorobenzene (HCB) induces inflammatory skin lesions and eosinophilic and granulomatous lung pathology as well as in vivo airways hyperresponsiveness to methacholine in the BN/SsNOlaHsd rat (Michielsen et al., Toxicol Appl Pharmacol 172:11-20, 2001), which are features of human Churg-Strauss syndrome (CSS), we have investigated whether HCB induced other features of CSS such as asthma and systemic vasculitis involving the heart and kidneys in this strain of rat. To this end, BN/SsNOlaHsd rats received control feed or feed supplemented with 450 mg/kg HCB. On days 6, 14 or 21, tracheas were isolated to assess non-specific in vitro airways hyperresponsiveness (AHR) to cumulative concentrations of arecoline and serotonin. In addition, lungs were lavaged to count and differentiate lavage cells, and skin, lungs, heart, kidneys, and lymph nodes were processed for histopathological investigation. HCB induced eosinophilic and granulomatous lung pathology in the BN/SsNOlaHsd rat, which became more severe with time and was associated with significant in vitro AHR to arecoline. Moreover, as in CSS-patients, systemic effects on spleen and lymph nodes were observed in HCB-fed BN/SsNOlaHsd rats, as well as development of skin lesions with vascular changes and eosinophilic infiltrates. In contrast, cardiac or renal involvement, frequently seen in CSS-patients, was not seen in HCB-fed rats. More importantly, there were no indications of necrotizing vasculitis, a hallmark feature of CSS, in the lungs and skin of BN/SsNOlaHsd rats. Thus, it is concluded that the persistent environmental pollutant HCB possibly induces a mild or early stage of CSS in the BN/SsNOlaHsd rat that may evolve into fully developed CSS after prolonged exposure to HCB. (orig.)

The environmental pollutant hexachlorobenzene causes eosinophilic and granulomatous inflammation and in vitro airways hyperreactivity in the Brown Norway rat

Energy Technology Data Exchange (ETDEWEB)

Michielsen, C; Zeamari, S; Vos, J [Department of Pathology, Faculty of Veterinary Medicine, Utrecht University (Netherlands); Leusink-Muis, A; Bloksma, N [Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences and Faculty of Biology, Utrecht University, Utrecht (Netherlands)

2002-05-01

Based on observations that the persistent environmental pollutant hexachlorobenzene (HCB) induces inflammatory skin lesions and eosinophilic and granulomatous lung pathology as well as in vivo airways hyperresponsiveness to methacholine in the BN/SsNOlaHsd rat (Michielsen et al., Toxicol Appl Pharmacol 172:11-20, 2001), which are features of human Churg-Strauss syndrome (CSS), we have investigated whether HCB induced other features of CSS such as asthma and systemic vasculitis involving the heart and kidneys in this strain of rat. To this end, BN/SsNOlaHsd rats received control feed or feed supplemented with 450 mg/kg HCB. On days 6, 14 or 21, tracheas were isolated to assess non-specific in vitro airways hyperresponsiveness (AHR) to cumulative concentrations of arecoline and serotonin. In addition, lungs were lavaged to count and differentiate lavage cells, and skin, lungs, heart, kidneys, and lymph nodes were processed for histopathological investigation. HCB induced eosinophilic and granulomatous lung pathology in the BN/SsNOlaHsd rat, which became more severe with time and was associated with significant in vitro AHR to arecoline. Moreover, as in CSS-patients, systemic effects on spleen and lymph nodes were observed in HCB-fed BN/SsNOlaHsd rats, as well as development of skin lesions with vascular changes and eosinophilic infiltrates. In contrast, cardiac or renal involvement, frequently seen in CSS-patients, was not seen in HCB-fed rats. More importantly, there were no indications of necrotizing vasculitis, a hallmark feature of CSS, in the lungs and skin of BN/SsNOlaHsd rats. Thus, it is concluded that the persistent environmental pollutant HCB possibly induces a mild or early stage of CSS in the BN/SsNOlaHsd rat that may evolve into fully developed CSS after prolonged exposure to HCB. (orig.)

The Significance of Mast Cells and Eosinophils Counts in Surgically Resected Appendix

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Ashwini Kolur

2014-06-01

Materials and Methods: The material for study consisted of appendix specimens received for histopathological examination in the Department of pathology. A 5 year study was conducted, 3 years retrospective and 2 years prospective. Results: Out of 777 cases studied the incidence of appendicitis is high, in the first and second decades of life and slightly higher in females. Recurrent appendicitis was more common when compared to other inflamed appendices. Conclusions: Eosinophil counts in all the layers were very high in acute eosinophilic appendicitis compared to normal appendices. A higher mast cell count was seen in acute eosinophilic appendicitis and recurrent appendicitis. No correlation was found between mast cell and eosinophilic density. Our observations support the allergic theory of appendicitis rather than the obstructive theory. [J Interdiscipl Histopathol 2014; 2(3.000: 150-153

BLOOD EOSINOPHIL NUMBERS AND ACTIVITY DURING 24 HOURS - EFFECTS OF TREATMENT WITH BUDESONIDE AND BAMBUTEROL

NARCIS (Netherlands)

WEMPE, JB; TAMMELING, EP; KOETER, GH; HAKANSSON, L; VENGE, P; POSTMA, DS

1992-01-01

The effects of the inhaled corticosteroid budesonide and the oral long-acting beta-agonist bambuterol on circadian variation of blood eosinophil numbers, serum levels of eosinophil cationic protein (ECP), serum eosinophil chemotactic activity (ECA), and serum neutrophil chemotactic activity (NCA)

Association of Blood Eosinophil and Blood Neutrophil Counts with Asthma Exacerbations in the Copenhagen General Population Study

DEFF Research Database (Denmark)

Vedel-Krogh, Signe; Nielsen, Sune Fallgaard; Lange, Peter

2017-01-01

BACKGROUND: Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated...... with the risk of asthma exacerbations among individuals with asthma from the general population. METHODS: From the Copenhagen General Population Study with 81351 participants, we included 4838 with self-reported asthma. We recorded baseline blood eosinophil and neutrophil counts, and asthma exacerbations during...... with blood eosinophil counts >0.29 × 10(9)/L (highest tertile) vs individuals with blood eosinophil counts

Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma.

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Gaurav, Rohit; Bewtra, Againdra K; Agrawal, Devendra K

2015-08-01

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β- and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very low expression of NOX1, NOX3, and NOX5 and no NOX4 mRNA. The level of NOX2 mRNA transcripts increased with disease severity in the eosinophils of subjects with asthma compared with healthy nonatopic volunteers. Change in granularity and size in eosinophils, but no change in intracellular ROS, was observed with phorbol myristate acetate (PMA). PMA, TGF-β, and eotaxin used the CLC3-dependent pathway to increase superoxide radicals. TGF-β and eotaxin induced CLC3-dependent chemotaxis of eosinophils. These findings support the requirement of CLC3 in the activation and migration of human blood eosinophils and may provide a potential novel therapeutic target to regulate eosinophil hyperactivity in allergic airway inflammation in asthma.

A Pilot Study of Omalizumab in Eosinophilic Esophagitis

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Loizou, Denise; Enav, Benjamin; Komlodi-Pasztor, Edina; Hider, Pamela; Kim-Chang, Julie; Noonan, Laura; Taber, Tabitha; Kaushal, Suhasini; Limgala, Renuka; Brown, Margaret; Gupta, Raavi; Balba, Nader; Goker-Alpan, Ozlem; Khojah, Amer; Alpan, Oral

2015-01-01

Eosinophilic disorders of the gastrointestinal tract are an emerging subset of immune pathologies within the spectrum of allergic inflammation. Eosinophilic Esophagitis (EoE), once considered a rare disease, is increasing in incidence, with a rate of over 1 in 10,000 in the US, for unknown reasons. The clinical management of EoE is challenging, thus there is an urgent need for understanding the etiology and pathophysiology of this eosinophilic disease to develop better therapeutic approaches. In this open label, single arm, unblinded study, we evaluated the effects of an anti-IgE treatment, omalizumab, on local inflammation in the esophagus and clinical correlates in patients with EoE. Omalizumab was administered for 12 weeks to 15 subjects with long standing EoE. There were no serious side effects from the treatment. Esophageal tissue inflammation was assessed both before and after therapy. After 3 months on omalizumab, although tissue Immunoglobulin E (IgE) levels were significantly reduced in all but two of the subjects, we found that full remission of EoE, which is defined as histologic and clinical improvement only in 33% of the patients. The decrease in tryptase-positive cells and eosinophils correlated significantly with the clinical outcome as measured by improvement in endoscopy and symptom scores, respectively. Omalizumab-induced remission of EoE was limited to subjects with low peripheral blood absolute eosinophil counts. These findings demonstrate that in a subset of EoE patients, IgE plays a role in the pathophysiology of the disease and that anti-IgE therapy with omalizumab may result in disease remission. Since this study is open label there is the potential for bias, hence the need for a larger double blind placebo controlled study. The data presented in this pilot study provides a foundation for proper patient selection to maximize clinical efficacy. Trial Registration ClinicalTrials.gov NCT01040598 PMID:25789989

Case series of eosinophilic meningoencephalitis from South India

Directory of Open Access Journals (Sweden)

Parameswaran K

2006-01-01

Full Text Available Eosinophilic meningoencephalitis (EM is a rare type of meningoencephalitis. The objective of this report is to describe a series of EM identified in a specific geographic area over a short period of time. Materials and Methods: This series of cases are described from a neurological center in Central Kerala occuring in the period between February 2004 and June 2006. Results: During this period we had identified ten patients (eight males and two females with EM. Their mean age was 37.1 years (range 15-60 years. Main symptomatologies were fever, severe headache, body pain, abdominal pain and arthralgia. One patient was in akinetic rigid state with coma. All patients had peripheral eosinophilia. The cerebrospinal fluid (CSF of all patients showed eosinophilic pleocytosis. The mean CSF white cell count was 588 cells. CSF differential count showed 50-70% eosinophils. CSF glucose levels were normal but proteins were markedly raised (mean CSF protein was 180 mg/dl. MRI brain showed T2 hyperintensities diffusely in periventricular white matter in the comatose patient. Contrast enhanced CT scan of the brain was normal in others. All eight male patients gave history of eating "raw flesh of Monitor Lizard" (Iguana some three to fourteen days prior to the onset of symptoms. There was no such history for the female patients. Considering the history of exposure and eosinophilic meningitis we suspected a meningoencephalitis with Angiostrongylus cantonensis and treated them with albendazole, steroid and other supportive measures. All of them recovered. Conclusion: Eosinophilic meningitis (EM is a rare condition and in this locality, a CNS infection with Agiostrongylus cantonensis is highly likely. AC is a parasite in monitor lizard. Human infection occurs from consumption of uncooked flesh or blood of infected lizards. Physicians need to maintain a high index of suspicion and enquire for any exposure to uncooked meat or blood of monitor lizard when faced with EM

Genetics Home Reference: eosinophil peroxidase deficiency

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... play a role in regulating inflammation by fighting microbial invaders. EPX gene mutations reduce or prevent eosinophil ... GINA) Turns 10 All Bulletins Features What are genome editing and CRISPR-Cas9? What is direct-to- ...

Expression and subcellular localization of the Qa-SNARE syntaxin17 in human eosinophils.

Science.gov (United States)

Carmo, Lívia A S; Dias, Felipe F; Malta, Kássia K; Amaral, Kátia B; Shamri, Revital; Weller, Peter F; Melo, Rossana C N

2015-10-01

SNARE members mediate membrane fusion during intracellular trafficking underlying innate and adaptive immune responses by different cells. However, little is known about the expression and function of these proteins in human eosinophils, cells involved in allergic, inflammatory and immunoregulatory responses. Here, we investigate the expression and distribution of the Qa-SNARE syntaxin17 (STX17) within human eosinophils isolated from the peripheral blood. Flow cytometry and a pre-embedding immunonanogold electron microscopy (EM) technique that combines optimal epitope preservation and secondary Fab-fragments of antibodies linked to 1.4 nm gold particles for optimal access to microdomains, were used to investigate STX17. STX17 was detected within unstimulated eosinophils. Immunogold EM revealed STX17 on secretory granules and on granule-derived vesiculotubular transport carriers (Eosinophil Sombrero Vesicles-EoSVs). Quantitative EM analyses showed that 77.7% of the granules were positive for STX17 with a mean±SEM of 3.9±0.2 gold particles/granule. Labeling was present on both granule outer membranes and matrices while EoSVs showed clear membrane-associated labeling. STX17 was also present in secretory granules in eosinophils stimulated with the cytokine tumor necrosis factor alpha (TNF-α) or the CC-chemokine ligand 11 CCL11 (eotaxin-1), stimuli that induce eosinophil degranulation. The number of secretory granules labeled for STX17 was significantly higher in CCL11 compared with the unstimulated group. The level of cell labeling did not change when unstimulated cells were compared with TNF-α-stimulated eosinophils. The present study clearly shows by immunanonogold EM that STX17 is localized in eosinophil secretory granules and transport vesicles and might be involved in the transport of granule-derived cargos. Copyright © 2015 Elsevier Inc. All rights reserved.

Eosinophils contribute to the resolution of lung-allergic responses following repeated allergen challenge.

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Takeda, Katsuyuki; Shiraishi, Yoshiki; Ashino, Shigeru; Han, Junyan; Jia, Yi; Wang, Meiqin; Lee, Nancy A; Lee, James J; Gelfand, Erwin W

2015-02-01

Eosinophils accumulate at the site of allergic inflammation and are critical effector cells in allergic diseases. Recent studies have also suggested a role for eosinophils in the resolution of inflammation. To determine the role of eosinophils in the resolution phase of the response to repeated allergen challenge. Eosinophil-deficient (PHIL) and wild-type (WT) littermates were sensitized and challenged to ovalbumin (OVA) 7 or 11 times. Airway inflammation, airway hyperresponsiveness (AHR) to inhaled methacholine, bronchoalveolar lavage (BAL) cytokine levels, and lung histology were monitored. Intracellular cytokine levels in BAL leukocytes were analyzed by flow cytometry. Groups of OVA-sensitized PHIL mice received bone marrow from WT or IL-10(-/-) donors 30 days before the OVA challenge. PHIL and WT mice developed similar levels of AHR and numbers of leukocytes and cytokine levels in BAL fluid after OVA sensitization and 7 airway challenges; no eosinophils were detected in the PHIL mice. Unlike WT mice, sensitized PHIL mice maintained AHR, lung inflammation, and increased levels of IL-4, IL-5, and IL-13 in BAL fluid after 11 challenges whereas IL-10 and TGF-β levels were decreased. Restoration of eosinophil numbers after injection of bone marrow from WT but not IL-10-deficient mice restored levels of IL-10 and TGF-β in BAL fluid as well as suppressed AHR and inflammation. Intracellular staining of BAL leukocytes revealed the capacity of eosinophils to produce IL-10. After repeated allergen challenge, eosinophils appeared not essential for the development of AHR and lung inflammation but contributed to the resolution of AHR and inflammation by producing IL-10. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue.

Science.gov (United States)

Bolus, W Reid; Gutierrez, Dario A; Kennedy, Arion J; Anderson-Baucum, Emily K; Hasty, Alyssa H

2015-10-01

Adipose tissue (AT) inflammation during obesity is mediated by immune cells and closely correlates with systemic insulin resistance. In lean AT, eosinophils are present in low but significant numbers and capable of promoting alternative macrophage activation in an IL-4/IL-13-dependent manner. In WT mice, obesity causes the proportion of AT eosinophils to decline, concomitant with inflammation and classical activation of AT macrophages. In this study, we show that CCR2 deficiency leads to increased eosinophil accumulation in AT. Furthermore, in contrast to WT mice, the increase in eosinophils in CCR2(-/-) AT is sustained and even amplified during obesity. Interestingly, a significant portion of eosinophils is found in CLSs in AT of obese CCR2(-/-) mice, which is the first time eosinophils have been shown to localize to these inflammatory hot spots. CCR2(-/-) bone marrow precursors displayed increased expression of various key eosinophil genes during in vitro differentiation to eosinophils, suggesting a potentially altered eosinophil phenotype in the absence of CCR2. In addition, the proportion of eosinophils in AT positively correlated with local expression of Il5, a potent eosinophil stimulator. The increase in eosinophils in CCR2(-/-) mice was detected in all white fat pads analyzed and in the peritoneal cavity but not in bone marrow, blood, spleen, or liver. In AT of CCR2(-/-) mice, an increased eosinophil number positively correlated with M2-like macrophages, expression of the Treg marker Foxp3, and type 2 cytokines, Il4, Il5, and Il13. This is the first study to link CCR2 function with regulation of AT eosinophil accumulation. © Society for Leukocyte Biology.

Imaginal diagnosis of eosinophilic granuloma of long bones

International Nuclear Information System (INIS)

Cui Fa; Cui Minyi

2006-01-01

Objective: To analyze the clinical and imaging features of eosinophilic granuloma of long bones so as to improve diagnosis accuracy of the disease. Methods: The clinic materials and imaging findings of 24 patients with eosinophilic granuloma of long bones proved by surgery or histopathology were analyzed retrospectively. All the patients received radiography; CT scan was performed in 6 cases; and MRI was done in 4 cases. Results: Fifteen patients out of 24 were male and 9 were female, with the average age 14. 7 years old. Solitary lesion was found in 22 cases, and multiple bone destruction was noted in 2 cases. There were 14 lesions located in femur; 5 in tibia; 3 in humer; and 2 in fibula. In total 16 lesions involved diaphysis and in 8 cases the metaphysis was invaded. Bone destruction, the changes of the adjacent cortex, periosteal reaction and soft tissue mass or swelling were demonstrated in images obtained. Conclusion: The imaging features in eosinophilic granuloma of long bones are characteristic. Careful and integrative analysis of imaging findings improves diagnosis accuracy of the disease. (authors)

Eosinophils, pruritus and psoriasis: effects of treatment with etretinate or cyclosporin-A.

Science.gov (United States)

Schopf, R E; Hultsch, T; Lotz, J; Bräutigam, M

1998-11-01

The antipsoriatic drugs cyclosporin A (CyA) and etretinate have been found to influence proinflammatory eosinophilic leukocytes and pruritus. We compared the number of blood eosinophils, concentration of serum eosinophil cationic protein (ECP), and pruritus in patients with psoriasis treated with either CyA or etretinate. Patients with psoriasis vulgaris were randomly assigned to treatment for 10 weeks with either CyA (n = 21) or etretinate (n = 10). The psoriasis area-and-severity index (PASI-score) and pruritus (according to a 0-3 scale) served as clinical parameters, the blood esosinophil counts (Coulter Counter) and the serum ECP (RIA, Pharmacia) as laboratory parameters. After CyA treatment the PASI-score amounted to 24 +/- 4%, after etretinate to 56 +/- 6% of the initial values (mean +/- SEM). One week after CyA treatment, esosinophils dropped from 190 +/- 21 to 137 +/- 16/microliter (P = 0.038, Wilcoxon test), after 10 weeks to 127 +/- 18/microliter (P = 0.006). By contrast, under etretinate blood eosinophil counts only changed marginally. Before treatment, ECP concentrations of 15.71 +/- 1.30 (CyA) and 15.3 +/- 5.53 micrograms/l (etretinate) were measured (normal range 3-16 micrograms/l), ECP remained constant under both CyA and etretinate or tended to increase after 10 weeks; about 50% of the patients exhibited elevated ECP concentrations. Pruritus diminished more with CyA than etretinate therapy. PASI-scores and pruritus were directly proportional. We conclude that treatment of psoriasis with CyA leads to a rapid drop of blood eosinophils and that the activation state of eosinophils does not decrease after antipsoriatic treatment. Pruritus in psoriasis is coupled to disease severity. The underlying antipsoriatic mechanisms of CyA may be linked to lowering the number of blood eosinophils.

Reduced expression of granule proteins during extended survival of eosinophils in splenocyte culture with GM-CSF.

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Ryu, Seul Hye; Na, Hye Young; Sohn, Moah; Han, Sun Murray; Choi, Wanho; In, Hyunju; Hong, Sookyung; Jeon, Hyejin; Seo, Jun-Young; Ahn, Jongcheol; Park, Chae Gyu

2016-05-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifaceted hematopoietic cytokine and the culture of mouse bone marrow with GM-CSF produces a variety of myeloid cells including granulocytes, macrophages, and dendritic cells. In the present study, we cultured mouse splenocytes with GM-CSF and examined the changes in hematopoietic cell populations over a week. Most of the splenic hematopoietic cells disappeared significantly from culture within 6days with or without the presence of GM-CSF. Among the splenic granulocyte populations, only eosinophils fully survived throughout the culture with GM-CSF for more than a week. During 10days of culture with GM-CSF, splenic eosinophils maintained their morphology as well as most of their surface molecules at high levels, including CCR3 and Siglec F. Meanwhile, the expression of mRNAs encoding major basic protein-1 (MBP-1) and eosinophil peroxidase (EPO), two major eosinophil-derived granule proteins, was diminished significantly from the cultured eosinophils. EPO assays also revealed that eosinophils in culture for more than 5days retained 30% or less EPO activity compared to those in uncultured splenocytes. In contrast, culture of splenocytes with GM-CSF did not change the capacity of eosinophils to migrate in response to eotaxin-1. Our results indicate that mouse splenic eosinophils are effectively cultured for lengthy periods while their expression of eosinophil-derived granule proteins is specifically suppressed. The relevance of these findings to eosinophilic inflammatory response is discussed. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Vasoactive intestinal peptide (VIP) binds to guinea pig peritoneal eosinophils: A single class of binding sites with low affinity and high capacity

International Nuclear Information System (INIS)

Sakakibara, H.; Shima, K.; Takamatsu, J.; Said, S.I.

1990-01-01

VIP binds to specific receptors on lymphocytes and mononuclear cells and exhibits antiinflammatory properties. Eosinophils (Eos) contribute to inflammatory reactions but the regulation of Eos function is incompletely understood. The authors examined the binding of monoradioiodinated VIP, [Tyr( 125 I) 10 ] VIP ( 125 I-VIP), to Eos in guinea pigs. The interaction of 125 i-VIP with Eos was rapid, reversible, saturable and linearly dependent on the number of cells. At equilibrium the binding was competitively inhibited by native peptide or by the related peptide helodermin. Scatchard analysis suggested the presence of a single class of VIP binding sites with a low affinity and a high capacity. In the presence of isobutyl-methylxanthine, VIP, PHI or helodermin did not stimulate cyclic AMP accumulation in intact Eos, while PGE 2 or 1-isoproterenol did. VIP also did not inhibit superoxide anion generation from Eos stimulated by phorbol myristate acetate. The authors conclude that: (1) VIP binds to low-affinity, specific sites on guinea pig peritoneal eosinophils; (2) this binding is not coupled to stimulation of adenylate cyclase; and (3) the possible function of these binding sites is at present unknown

Impaired esophageal motor function in eosinophilic esophagitis

Directory of Open Access Journals (Sweden)

Cecilio Santander

2015-10-01

Full Text Available Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.

High resolution autoradiographic studies of RNA, protein and DNA synthesis during human eosinophil granulocytopoiesis

International Nuclear Information System (INIS)

Wickramasinghe, S.N.; Hughes, M.

1978-01-01

Human bone marrow cells which had been incubated with [ 3 H] uridine or [ 3 H]leucine for 1 h were studied using the technique of electron microscope-autoradiography. The autoradiographs revealed the presence of newly-synthesized RNA and protein molecules within or on a proportion of (1) the primary and secondary granules in all classes of eosinophil precursors and (2) the secondary granules in eosinophil granulocytes. It is suggested that the granule-associated RNA molecules may be concerned with the synthesis of at least some of the new protein molecules which were incorporated into the limiting membrane or substance of eosinophil granules long after the immature primary granule stage. Studies of eosinophil precursors which had been incubated with [ 3 H]thymidine for 1 h showed that the eosinophil granules did not label with this DNA precursor. (author)

Suppressive effects of primed eosinophils on single epicutaneous sensitization through regulation of dermal dendritic cells.

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Lin, Jing-Yi; Ta, Yng-Cun; Liu, I-Lin; Chen, Hsi-Wen; Wang, Li-Fang

2016-07-01

Eosinophils are multifunctional innate immune cells involved in many aspects of innate and adaptive immunity. Epicutaneous sensitization with protein allergen is an important sensitization route for atopic dermatitis. In this study, using a murine single protein-patch model, we show that eosinophils of a primed status accumulate in draining lymph nodes following single epicutaneous sensitization. Further, depletion of eosinophils results in enhancement of the induced Th1/Th2 immune responses, whereas IL-5-induced hypereosinophilia suppresses these responses. Mechanistically, primed eosinophils cause a reduction in the numbers and activation status of dermal dendritic cells in draining lymph nodes. Collectively, these results demonstrate that primed eosinophils exert suppressive effects on single epicutaneous sensitization through regulation of dermal dendritic cells. Thus, these findings highlight the critical roles of eosinophils in the pathogenesis of atopic dermatitis with important clinical implications for the prevention of allergen sensitization. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A pediatric case of Fascioliasis with eosinophilic pneumonia.

Science.gov (United States)

Bayhan, Gülsüm İclal; Batur, Abdulsamet; Taylan-Özkan, Ayşegül; Demirören, Kaan; Beyhan, Yunus Emre

2016-01-01

Fasciolia spp. are common trematode infestations worldwide. Fasciolia spp. may lead to hepatic diseases in the acute phase and may cause biliary diseases in the chronic phase. In addition, Fasciolia spp. may rarely cause extrahepatic signs and symptoms. The clinical manifestations of fascioliasis are divided into three groups: typical, atypical, and ectopic. Eosinophilic pneumonia is an atypical presentation of acute fascioliasis and it has been reported very rarely. Herein, we report a boy with marked blood eosinophilia and eosinophilic pneumonia who was diagnosed with fascioliasis by serologic tests and abdominal USG. The patient recovered completely following triclabendazole treatment.

Eosinophils promote generation and maintenance of immunoglobulin-A-expressing plasma cells and contribute to gut immune homeostasis.

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Chu, Van Trung; Beller, Alexander; Rausch, Sebastian; Strandmark, Julia; Zänker, Michael; Arbach, Olga; Kruglov, Andrey; Berek, Claudia

2014-04-17

Although in normal lamina propria (LP) large numbers of eosinophils are present, little is known about their role in mucosal immunity at steady state. Here we show that eosinophils are needed to maintain immune homeostasis in gut-associated tissues. By using eosinophil-deficient ΔdblGATA-1 and PHIL mice or an eosinophil-specific depletion model, we found a reduction in immunoglobulin A(+) (IgA(+)) plasma cell numbers and in secreted IgA. Eosinophil-deficient mice also showed defects in the intestinal mucous shield and alterations in microbiota composition in the gut lumen. In addition, TGF-β-dependent events including class switching to IgA in Peyer's patches (PP), the formation of CD103(+) T cells including Foxp3(+) regulatory (Treg), and also CD103(+) dendritic cells were disturbed. In vitro cultures showed that eosinophils produce factors that promote T-independent IgA class switching. Our findings show that eosinophils are important players for immune homeostasis in gut-associated tissues and add to data suggesting that eosinophils can promote tissue integrity. Copyright © 2014 Elsevier Inc. All rights reserved.

Suppressions of Serotonin-Induced Increased Vascular Permeability and Leukocyte Infiltration by Bixa orellana Leaf Extract

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Yoke Keong Yong

2013-01-01

Full Text Available The aim of the present study was to evaluate the anti-inflammatory activities of aqueous extract of Bixa orellana (AEBO leaves and its possible mechanisms in animal models. The anti-inflammatory activity of the extract was evaluated using serotonin-induced rat paw edema, increased peritoneal vascular permeability, and leukocyte infiltrations in an air-pouch model. Nitric oxide (NO, indicated by the sum of nitrites and nitrates, and vascular growth endothelial growth factor (VEGF were measured in paw tissues of rats to determine their involvement in the regulation of increased permeability. Pretreatments with AEBO (50 and 150 mg kg−1 prior to serotonin inductions resulted in maximum inhibitions of 56.2% of paw volume, 45.7% of Evans blue dye leakage in the peritoneal vascular permeability model, and 83.9% of leukocyte infiltration in the air-pouch model. 57.2% maximum inhibition of NO and 27% of VEGF formations in rats’ paws were observed with AEBO at the dose of 150 mg kg−1. Pharmacological screening of the extract showed significant (P<0.05 anti-inflammatory activity, indicated by the suppressions of increased vascular permeability and leukocyte infiltration. The inhibitions of these inflammatory events are probably mediated via inhibition of NO and VEGF formation and release.

Increased Activity and Apoptosis of Eosinophils in Blister Fluids, Skin and Peripheral Blood of Patients with Bullous Pemphigoid.

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Engmann, Judith; Rüdrich, Urda; Behrens, Georg; Papakonstantinou, Eleni; Gehring, Manuela; Kapp, Alexander; Raap, Ulrike

2017-04-06

Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more common in elderly individuals. The aim of this study was to determine the functional activity of eosinophils in patients with BP compared with healthy donors. Blood, skin and blister-derived eosinophils were strongly activated in patients with BP, seen by increased surface expression of CD69 compared with controls. CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1×106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1α in BP blister fluids. Apoptosis in cultivated BP eosinophils was increased and accompanied by enhanced surface externalization of CD95. Caspase 3 positive eosinophils in lesional BP skin and blister fluid also showed the initiation of apoptosis. These results reveal novel pathophysiological aspects of BP, with a strong activation pattern and increased apoptosis of eosinophils in the peripheral blood, skin and blister fluids.

Anti-IL-5 attenuates activation and surface density of β2-integrins on circulating eosinophils after segmental antigen challenge

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Johansson, Mats W.; Gunderson, Kristin A.; Kelly, Elizabeth A. B.; Denlinger, Loren C.; Jarjour, Nizar N.; Mosher, Deane F.

2013-01-01

Background IL-5 activates αMβ2 integrin on blood eosinophils in vitro. Eosinophils in bronchoalveolar lavage (BAL) following segmental antigen challenge have activated β2-integrins. Objective To identify roles for IL-5 in regulating human eosinophil integrins in vivo. Methods Blood and BAL eosinophils were analyzed by flow cytometry in ten subjects with allergic asthma who underwent a segmental antigen challenge protocol before and after anti-IL-5 administration. Results Blood eosinophil reactivity with monoclonal antibody (mAb) KIM-127, which recognizes partially activated β2-integrins, was decreased after anti-IL-5. Before anti-IL-5, surface densities of blood eosinophil β2, αM, and αL integrin subunits increased modestly post-challenge. After anti-IL-5, such increases did not occur. Before or after anti-IL-5, surface densities of β2,αM, αL, and αD and reactivity with KIM-127 and mAb CBRM1/5, which recognizes high-activity αMβ2, were similarly high on BAL eosinophils 48 h post-challenge. Density and activation state of β1-integrins on blood and BAL eosinophils were not impacted by anti-IL-5, even though anti-IL-5 ablated a modest post-challenge increase on blood or BAL eosinophils of P-selectin glycoprotein ligand-1 (PSGL-1), a receptor for P-selectin that causes activation of β1-integrins. Forward scatter of blood eosinophils post-challenge was less heterogeneous and on the average decreased after anti-IL-5; however, anti-IL-5 had no effect on the decreased forward scatter of eosinophils in post-challenge BAL compared to eosinophils in blood. Blood eosinophil KIM-127 reactivity at the time of challenge correlated with the percentage of eosinophils in BAL post-challenge. Conclusion and Clinical Relevance IL-5 supports a heterogeneous population of circulating eosinophils with partially activated β2-integrins and is responsible for upregulation of β2-integrins and PSGL-1 on circulating eosinophils following segmental antigen challenge but has

The effects of Strongylus vulgaris parasitism on eosinophil distribution and accumulation in equine large intestinal mucosa.

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Rötting, A K; Freeman, D E; Constable, P D; Moore, R M; Eurell, J C; Wallig, M A; Hubert, J D

2008-06-01

Eosinophilic granulocytes have been associated with parasite or immune-mediated diseases, but their functions in other disease processes remain unclear. Cause and timing of eosinophil migration into the equine gastrointestinal mucosa are also unknown. To determine the effects of intestinal parasitism on eosinophils in equine large intestinal mucosa. Large intestinal mucosal samples were collected from horses and ponies (n = 16) from the general veterinary hospital population, ponies (n = 3) raised in a parasite-free environment, ponies experimentally infected with 500 infective Strongylus vulgaris larvae and treated with a proprietary anthelmintic drug (n = 14), and a similar group of ponies (n = 7) that received no anthelmintic treatment. Total eosinophil counts and eosinophil distribution in the mucosa were determined by histological examination. A mixed model analysis was performed and appropriate Bonferroni adjusted P values used for each family of comparisons. Pvulgaris and those raised in a parasite-free environment. Experimental infection with S. vulgaris, with or without subsequent anthelmintic treatment, did not change eosinophil counts, and counts were similar to those for horses from the general population. Migration of eosinophils to the equine large intestinal mucosa appears to be independent of exposure to parasites. Large intestinal mucosal eosinophils may have more functions in addition to their role in defence against parasites.

The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking

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Schratl, Petra; Royer, Julia F; Kostenis, Evi

2007-01-01

of DP has remained unclear. We report in this study that, in addition to CRTH2, the DP receptor plays an important role in eosinophil trafficking. First, we investigated the release of eosinophils from bone marrow using the in situ perfused guinea pig hind limb preparation. PGD2 induced the rapid......Prostaglandin (PG) D2 is a major mast cell product that acts via two receptors, the D-type prostanoid (DP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptors. Whereas CRTH2 mediates the chemotaxis of eosinophils, basophils, and Th2 lymphocytes, the role...

Eosinophilic meningitis caused by infection of Angiostrongylus cantonensis in a traveler

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GUAN Hongzhi; HOI Chupeng; CUI Liying; CHEN Lin

2013-01-01

A 55 - year - old female traveler returning from South China with acute onset of meningitis, presenting with eosinophilic pleocytosis in the cerebrospinal fluid was reported. The etiological diagnosis of angiostrongyliasis was confirmed by detection of specific serum antibody against Angiostrongylus cantonensis. Angiostrongyliasis should be considered as a major differential diagnosis for eosinophilic meningitis in the travelers to endemic regions.

Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy

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Melo, Rossana C.N., E-mail: rossana.melo@ufjf.edu.br [Laboratory of Cellular Biology, Department of Biology, ICB, Federal University of Juiz de Fora, UFJF, Rua José Lourenço Kelmer, Juiz de Fora, MG 36036-900 (Brazil); Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215 (United States); Weller, Peter F. [Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215 (United States)

2016-10-01

Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles – EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. - Highlights: • Application of EM to understand the complex secretory pathway in human eosinophils. • EM techniques reveal an active vesicular system associated with secretory granules. • Tubular vesicles are involved in the transport of granule-derived immune mediators.

Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy

International Nuclear Information System (INIS)

Melo, Rossana C.N.; Weller, Peter F.

2016-01-01

Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles – EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. - Highlights: • Application of EM to understand the complex secretory pathway in human eosinophils. • EM techniques reveal an active vesicular system associated with secretory granules. • Tubular vesicles are involved in the transport of granule-derived immune mediators.

Predictive value of eosinophils and neutrophils on clinical effects of ICS in COPD

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Hartjes, Floor J; Vonk, Judith M; Faiz, Alen

2018-01-01

BACKGROUND AND OBJECTIVE: Inflammation is present to a variable degree and composition in patients with COPD. This study investigates associations between both eosinophils and neutrophils in blood, sputum, airway wall biopsies and bronchoalveolar lavage (BAL) and their potential use as biomarkers...... and BAL were evaluated at baseline. In addition, at baseline, 6 and 30 months, forced expiratory flow in 1 s (FEV1 ), residual volume/total lung capacity (hyperinflation) and Clinical COPD Questionnaire were evaluated. RESULTS: Cross-sectional analyses at baseline showed that higher blood eosinophils were...... significantly associated with higher eosinophil counts in sputum, biopsies and BAL. However, blood neutrophils did not significantly correlate with neutrophil counts in the other compartments. Baseline eosinophils and neutrophils, in whichever compartment measured, did not predict longitudinal FEV1 changes...

Blood eosinophil counts for the prediction of the severity of exercise-induced bronchospasm in asthma.

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Koh, Y I; Choi, S

2002-02-01

It has been suggested that airway eosinophilic inflammation is associated with the severity of exercise-induced bronchospasm (EIB). Blood eosinophils are known to be an indirect marker of airway inflammation in asthma. The aim of this study is to investigate that a simple and easy blood test for blood eosinphil counts may predict the severity of EIB in asthma. Seventy-seven men with perennial asthma (age range 18-23 years) were included. Lung function test, skin prick test, and blood tests for eosinophils counts and total IgE levels were performed. Methacholine bronchial provocation test and, 24 h later, free running test were carried out. EIB was defined as a 15% reduction or more in post-exercise FEV1 compared with pre-exercise FEV1 value. Atopy score was defined as a sum of mean wheal diameters to allergens. EIB was observed in 60 (78%) of 77 subjects. Asthmatics with EIB showed significantly increased percentages of eosinophils (P 700 microl(-1) (36.9 +/- 12.7%) had significantly greater maximal % fall in FEV1 after exercise than asthmatics with eosinophils of 350 microl(-1) yielded the specificity of 88% and positive predictive value of 93% for the presence of EIB. When a multiple regression analysis of maximal % fall in FEV1 according to log eosinophil counts, log PC20, log IgE and atopy score was performed, only blood eosinophil counts were significant factor contributing to the maximal % fall in FEV1 after exercise. These findings not only suggest that a simple blood test for eosinophils may be useful in the prediction of the severity of EIB, but also reinforce the view that airway eosinophilic inflammation may play a major role in EIB in asthma.

Pre-operative irradiation of eosinophilic granuloma in the parotid area

International Nuclear Information System (INIS)

Kitahara, Satoshi; Toda, Yukio; Nakajima, Hisami; Takeyama, Isamu; Sodemoto, Yukio; Endo, Masaru

1983-01-01

Eosinophilic granuloma is thought to originate in the reticuloendothelial system and cannot clearly be distinguished from the surrounding tissue during operation. An eosinophilic granuloma in the parotid area was removed after 25 days of irradiation at a dosage of 10.0 Gy per 3 days. A thin capsule of connective tissue was observed after the tumor was cut in half. Then, histopathological studies were performed on this connective tissue to determine the effect of the irradiation. Histopathologically, at the periphery of the tissue, atrophy of lymphocytes and destruction of the lymphoid tissue, which were thought to result in an increase in the connective tissue, were observed. It was concluded that a small dose of pre-operative radiation on eosinophilic granuloma in the parotid area made the tumor small and produced a capsule around the tumor. (author)

Case report 342: Eosinophilic granuloma of the right iliac wing

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Schlesinger, A.E.; Glass, R.B.J.; Fernbach, S.K.; Young, S.

1986-01-01

In summary, this case demonstrates that eosinophilic granuloma may present with findings on CT usually associated with aggressive malignant lesions, while plain films may show the same lesion to have the unequivocal appearance of a benign lesion. It is important, therefore, that eosinophilic granuloma be considered in the differential diagnosis of solitary bone lesions with extraosseous extension, extensive destruction of the cortex and associated periosteal reaction. A local biopsy, as opposed to wide excision, should be performed for diagnosis, prior to any therapy. Of at least equal significance, it is obvious from this case that plain films in many instances still maintain their importance and with few exceptions should be obtained prior to the CT study. In this instance the diagnosis of a benign disorder and even the specific diagnoses of eosinophilic, granuloma was suggested with confidence because of the plain films. (orig.)

Idiopathic eosinophilic parotitis in an eight-year-old boy: a case report

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Gelardi Matteo

2011-08-01

Full Text Available Abstract Introduction A number of medical conditions, some of them recently reported, are associated with an increased production of eosinophils. We report the first case of eosinophilic parotitis in the literature. Case presentation The patient was an eight-year-old Caucasian boy who presented with a two-year history of recurring acute parotitis with no fever. He had had a total of five episodes with no response to antibiotics, but remission had been achieved with oral corticosteroid therapy. We performed allergy tests for inhalant and food allergens and for haptens, but the results were all negative. The results of echography ruled out sialodochitis. Instead, a swab from the parotid duct led to the detection of a high number of eosinophils. Conclusions This report is first in the literature to describe a case of eosinophilic parotitis, and we suggest that a cytological assessment, which is quite simple yet rarely used by physicians, be performed when patients with parotitis of uncertain origin are under evaluation.

Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.

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Lu Huang

2015-12-01

Full Text Available It has become increasingly clear that the functions of eosinophils extend beyond host defense and allergy to metabolism and tissue regeneration. These influences have strong potential to be relevant in worm infections in which eosinophils are prominent and parasites rely on the host for nutrients to support growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that IL-4 and eosinophils are necessary for normal larval growth and that eosinophils from IL-4 competent mice are sufficient to support growth. The eosinophil-mediated effect operates in the absence of adaptive immunity. Following invasion by newborn larvae, host gene expression in skeletal muscle was compatible with a regenerative response and a shift in the source of energy in infected tissue. The presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4 and phosphorylation of Akt were observed in nurse cells, consistent with enhancement of glucose uptake and glycogen storage by larvae that is known to occur. The data are consistent with a mechanism in which eosinophils promote larval growth by an IL-4 dependent mechanism that limits local interferon-driven responses that otherwise alter nutrient metabolism in infected muscle. Our findings document a novel interaction between parasite and host in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth.

Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.

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Huang, Lu; Beiting, Daniel P; Gebreselassie, Nebiat G; Gagliardo, Lucille F; Ruyechan, Maura C; Lee, Nancy A; Lee, James J; Appleton, Judith A

2015-12-01

It has become increasingly clear that the functions of eosinophils extend beyond host defense and allergy to metabolism and tissue regeneration. These influences have strong potential to be relevant in worm infections in which eosinophils are prominent and parasites rely on the host for nutrients to support growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that IL-4 and eosinophils are necessary for normal larval growth and that eosinophils from IL-4 competent mice are sufficient to support growth. The eosinophil-mediated effect operates in the absence of adaptive immunity. Following invasion by newborn larvae, host gene expression in skeletal muscle was compatible with a regenerative response and a shift in the source of energy in infected tissue. The presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4) and phosphorylation of Akt were observed in nurse cells, consistent with enhancement of glucose uptake and glycogen storage by larvae that is known to occur. The data are consistent with a mechanism in which eosinophils promote larval growth by an IL-4 dependent mechanism that limits local interferon-driven responses that otherwise alter nutrient metabolism in infected muscle. Our findings document a novel interaction between parasite and host in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth.

Anterior ischaemic optic neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a case report and review of the literature.

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Padovano, Ilaria; Pazzola, Giulia; Pipitone, Nicolò; Cimino, Luca; Salvarani, Carlo

2014-01-01

We report a 62-year-old man with mild fever, headache and acute visual loss in his right eye due to anterior ischaemic optic neuropathy (AION), followed a few days later by pain in the legs and left arm associated with numbness and weakness. Giant cell arteritis complicated by AION was suspected at the beginning and high-dose oral glucocorticoids were started. However, on the basis of the past medical history of nasal polyposis, asthma, and hypereosynophilia as well as of further investigations (biopsy of the nasal mucosa showing granulomatous inflammation with a rich eosinophilic infiltrate, electromyography demonstrating, mononeuritis multiplex and positive p-ANCA), eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, was diagnosed. Because visual acuity in the right eye deteriorated despite glucocorticoid therapy, pulse intravenous cyclophosphamide was started, subsequently replaced by oral azathioprine, while prednisone was slowly tapered. This treatment led to gradual improvement of the neurological symptoms, whereas the right visual impairment remained unchanged. EGPA-related AION is an uncommon lesion that is probably due to vasculitic involvement of posterior ciliary and/or chorioretinal arteries. The prognosis of established AION is poor for the affected eye, even when glucocorticoid treatment is started immediately. However, early recognition of AION and prompt aggressive treatment with high-dose glucocorticoids plus cyclophosphamide can prevent visual loss in the unaffected eye.

Hematemesis as Initial Presentation in a 10-Week-Old Infant with Eosinophilic Gastroenteritis

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Varun Shetty

2017-01-01

Full Text Available Eosinophilic gastroenteritis is a rare condition characterized by eosinophilic inflammation in the gastrointestinal tract resulting in a variety of gastrointestinal symptoms. There is currently a dearth of information on this topic in the pediatric literature, as very few cases have been reported. In this report, we present a case of eosinophilic gastroenteritis in a 10-week-old patient with initial presenting symptom of hematemesis. To our knowledge, this is the youngest case reported in the literature and is unique in its initial presentation.

SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice.

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Percopo, Caroline M; Brenner, Todd A; Ma, Michelle; Kraemer, Laura S; Hakeem, Reem M A; Lee, James J; Rosenberg, Helene F

2017-01-01

Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45 + CD11c - SiglecF + Gr1 hi ). SiglecF + Gr1 hi eosinophils, distinct from the canonical SiglecF + Gr1 - eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX -/- and MBP-1 -/- ) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1 + neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF + Gr1 hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G + Although indistinguishable from the more-numerous SiglecF + Gr1 - eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF + Gr1 hi eosinophil population (at 3.9 and 4.8 pg/10 6 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/10 6 cells). Interestingly, bone marrow-derived (SiglecF + ), cultured eosinophils include a more substantial Gr1 + subpopulation (∼50%); Gr1 + bmEos includes primarily a single Ly6C + and a smaller, double-positive (Ly6C + Ly6G + ) population. Taken together, our findings characterize a distinct SiglecF + Gr1 hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF + Gr1 hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. © Society for Leukocyte Biology.

A Case Report of Eosinophilic Esophagitis Accompanying Hypereosinophilic Syndrome

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Mahreema Jawairia

2012-01-01

Full Text Available Hypereosinophilic syndrome is a blood disorder characterized by the overproduction of eosinophils in the bone marrow with persistent peripheral eosinophilia, associated with organ damage by the release of eosinophilic mediators. Although HES can involve multiple organ systems, GI tract involvement is very rare. Few cases of HES presenting with gastritis or enteritis have been reported worldwide. To date, HES presenting with esophagus involvement has only been reported once. Here, we present a 39-year-old Hispanic female patient with history of HES presenting with complaints of dysphagia and generalized pruritus.

Elevated Systemic Levels of Eosinophil, Neutrophil, and Mast Cell Granular Proteins in Strongyloides Stercoralis Infection that Diminish following Treatment.

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Rajamanickam, Anuradha; Munisankar, Saravanan; Bhootra, Yukthi; Dolla, Chandra Kumar; Nutman, Thomas B; Babu, Subash

2018-01-01

Infection with the helminth parasite Strongyloides stercoralis ( Ss ) is commonly clinically asymptomatic that is often accompanied by peripheral eosinophilia. Granulocytes are activated during helminth infection and can act as immune effector cells. Plasma levels of eosinophil and neutrophil granular proteins convey an indirect measure of granulocyte degranulation and are prominently augmented in numerous helminth-infected patients. In this study, we sought to examine the levels of eosinophil, neutrophil, and mast cell activation-associated granule proteins in asymptomatic Ss infection and to understand their kinetics following anthelmintic therapy. To this end, we measured the plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, neutrophil elastase, myeloperoxidase, neutrophil proteinase-3, mast cell tryptase, leukotriene C4, and mast cell carboxypeptidase-A3 in individuals with asymptomatic Ss infection or without Ss infection [uninfected (UN)]. We also estimated the levels of all of these analytes in infected individuals following definitive treatment of Ss infection. We demonstrated that those infected individuals have significantly enhanced plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, elastase, myeloperoxidase, mast cell tryptase, leukotriene C4, and carboxypeptidase-A3 compared to UN individuals. Following the treatment of Ss infection, each of these granulocyte-associated proteins drops significantly. Our data suggest that eosinophil, neutrophil, and mast cell activation may play a role in the response to Ss infection.

Eosinophilic spleen colonies are produced in rat-marrow-transplanted but not in murine-marrow-transplanted mice

International Nuclear Information System (INIS)

Szabo, L.G.; Kelemen, E.

1988-01-01

Differential counts of about 5000 splenic clusters and colonies developing in whole-body-irradiated mice and rats were made, using semi-serial histological sections prepared 9 to 12 d after transplantation with bone marrow haemopoietic cells. The investigated mouse and rat spleens were from syngeneically, allogeneically, or xenogeneically transplanted recipients. Splenic eosinophil clusters were always found when rat eosinophil-producing progenitors were present in the inoculum, whereas murine inocula failed to produce splenic eosinophilic clusters even in the syngeneic mouse. The limiting factor in the production pf splenic eosinophilic clusters was the appropriate donor progenitor/committed stem cell itself. Changes in the percentages of eosinophil clusters with the number of injected cells and with increased doses of irradiation, as well as formation of rat eosinophil colonies in mice, as against mainly clusters in rats, themselves show that regulatory mechanisms of the recipients also play a role. These regulatory mechanisms cannot be attributed to the splenic microenvironment. (author)

Eosinophil inversely associates with type 2 diabetes and insulin resistance in Chinese adults.

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Liying Zhu

Full Text Available CONTEXT: Limited population-based study focused on relationship between eosinophil and type 2 diabetes (T2D. OBJECTIVES: We aimed to evaluate the relationship between peripheral eosinophil percentage and glucose metabolism and insulin resistance in a large sample size of Chinese population aged 40 and older. DESIGN AND METHODS: A cross-sectional study was performed among 9,111 Chinese adults including 3,561 men and 5,550 women. The glucose metabolism status was confirmed by 75-g oral glucose tolerance test. Homeostasis model assessment of insulin resistance index and serum insulin levels were used to evaluate insulin resistance. Homeostasis model assessment-B was used to evaluate β cell function. RESULTS: The average age of participants was 58.5 years. The prevalence of T2D decreased across the tertiles of eosinophil percentage (21.3%, 18.2% and 16.9%, P<0.0001. Each one tertile increase of eosinophil percentage inversely associated with risk of T2D when referred not only to normal glucose tolerance (NGT (odds ratio (OR 0.81, 95% CI 0.76-0.87, P< 0.0001, but also to impaired glucose regulation (OR 0.89, 95% CI 0.83-0.97, P = 0.006, respectively, after adjustment for the confounding factors. Compared with the first tertile, the third tertile of eosinophil percentage associated with a 23% decrease of insulin resistance in NGT participants after full adjustments (P = 0.005. Each 1-standard deviation of increment of eosinophil percentage associated with a 37% decrease of insulin resistance (P = 0.005. CONCLUSIONS: Higher peripheral eosinophil percentage was associated with decreased risk of T2D. The inverse relation to insulin resistance was detected in NGT participants.

IL-5 Induces Suspended Eosinophils to Undergo Unique Global Reorganization Associated with Priming

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Han, Shih-Tsung

2014-01-01

The experiments described herein define a unique program of polarization of suspended human eosinophils stimulated with IL-5 family cytokines. We found that eosinophil granules and the nucleus move in opposite directions to form, respectively, a granular compartment and the nucleopod, a specialized uropod occupied by the nucleus and covered with adhesion receptors, including P-selectin glycoprotein ligand-1, CD44, and activated αMβ2 integrin. Ligated IL-5 family receptors localize specifically at the tip of the nucleopod in proximity to downstream signaling partners Janus tyrosine kinase 2, signal transducer and activator of transcription-1 and -5, and extracellular signal–regulated kinase. Microscopy and effects of cytochalasin B and nocodazole indicate that remodeling of filamentous actin and reorientation of the microtubule network are required for eosinophil polarization and nucleopod formation. IL-5 induces persistent polarization and extracellular signal–regulated kinase redistribution that are associated with eosinophil priming, a robust response on subsequent stimulation with N-formyl-methionyl-leucyl-phenylalanine. Global reorganization of cytoskeleton, organelles, adhesion receptors, and signaling molecules likely facilitates vascular arrest, extravasation, migration, granule release, and survival of eosinophils entering inflamed tissues from the bloodstream. PMID:24156300

Role of the eosinophil in serum-mediated adherence of equine leukocytes to infective larvae of Strongylus vulgaris.

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Klei, T R; Chapman, M R; Dennis, V A

1992-06-01

The adherence of equine leukocytes to Strongylus vulgaris infective larvae (L3) in the presence of normal and immune sera was examined in vitro. Immune sera promoted adherence of buffy coat cells from ponies with S. vulgaris-induced eosinophilia (eosinophilic ponies) to S. vulgaris L3. However, eosinophils in the buffy coat cells were the predominant adherent cell type. Studies using leukocyte populations enriched for eosinophils, neutrophils, and mononuclear cells from eosinophilic ponies support the observations using buffy coat cells that eosinophils were the main effector cells. Adherent eosinophils from eosinophilic ponies immobilized L3. Neutrophils were less adherent and did not immobilize L3. Mononuclear cells failed to adhere. Normal eosinophils from strongly-naive ponies did not immobilize S. vulgaris L3 in the presence of immune serum, suggesting the in vivo activation of eosinophils in eosinophilic animals. Immune serum promoted less adherence of buffy coat cells to Strongylus edentatus or mixed species of Cyathostominae L3, suggesting that the serum-mediated cellular adherence phenomenon was species-specific. Normal serum promoted less cellular adherence to S. vulgaris L3 than immune serum. The adherence mediated by normal serum was removed by heat inactivation, suggesting that this nonspecific phenomenon was a complement-mediated reaction. Immune globulins promoted reactions similar to that seen using heat-inactivated immune serum, whereas normal globulins did not promote adherence. Immune globulins absorbed with pieces of S. vulgaris adult worms did not promote the adherence of buffy coat cells to S. vulgaris L3, suggesting that adult and L3 stages share antigens important in this phenomenon that resulted in the removal of specific adherence antibody during absorption.

Infiltration SuDS Map

OpenAIRE

Dearden, Rachel

2012-01-01

Infiltration SuDS are sustainable drainage systems (SuDS) that allow surface water to infiltrate to the ground. Examples include soakaways, infiltration basins, infiltration trenches and permeable pavements. Before planning to install Infiltration SuDS, the suitability of the ground should be assessed. The British Geological Survey has developed a bespoke Infiltration SuDS Map that enables a preliminary assessment of the suitability of the ground for infiltration SuDS. Th...

In vitro progression of artificial white spot lesions sealed with an infiltrant resin.

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Gelani, R; Zandona, A F; Lippert, F; Kamocka, M M; Eckert, G

2014-01-01

This study assessed the ability of an infiltrant resin (Icon, DMG Chemisch-Pharmazeutische Fabrik GmbH, Hamburg, Germany) to prevent artificial lesion progression in vitro when used to impregnate white spot lesions and also assessed the effect of saliva contamination on resin infiltration. Enamel specimens (n=252) were prepared and covered with nail varnish, leaving a window of sound enamel. After demineralization (pH 5.0; four weeks), specimens were divided into six groups (n=42 per group): group 1, 2% fluoride gel (positive control); group 2, resin infiltrant; group 3, resin infiltrant + fluoride gel; group 4, no treatment (negative control); group 5, resin infiltrant application after saliva contamination; and group 6, resin infiltrant + fluoride gel after saliva contamination. Specimens from each group were cut perpendicular to the surface, and one-half of each specimen was exposed to a demineralizing solution for another four weeks. The other half was set aside as a record of initial lesion depth and was used later in the determination of lesion progression. Lesion progression and infiltrant penetration were measured using confocal laser scanning microscopy (CLSM) and transverse microradiography (TMR). For lesion depth, based on CLSM, groups 2 and 3 showed the least changes when submitted to demineralization challenge, followed by group 1, then groups 5 and 6, and finally group 4. There were no significant differences between groups 2 and 3 or groups 5 and 6 in their ability to inhibit further lesion progression (p<0.05). Based on TMR, groups 2 and 3 also showed the fewest changes when submitted to demineralization challenge, followed by group 5, then groups 1 and 6, and finally group 4. In terms of mineral loss as measured by TMR, all groups that contained fluoride (groups 1, 3, and 6) show less percentage change in mineral loss than the groups that did not contain fluoride (groups 2, 4, and 5). It can be concluded that infiltrant penetration into early

Combination of CD157 and FLAER to Detect Peripheral Blood Eosinophils by Multiparameter Flow Cytometry.

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Carulli, Giovanni; Marini, Alessandra; Sammuri, Paola; Domenichini, Cristiana; Ottaviano, Virginia; Pacini, Simone; Petrini, Mario

2015-01-01

The identification of eosinophils by flow cytometry is difficult because most of the surface antigens expressed by eosinophils are shared with neutrophils. Some methods have been proposed, generally based on differential light scatter properties, enhanced autofluorescence, lack of CD16 or selective positivity of CD52. Such methods, however, show several limitations. In the present study we report a novel method based on the analysis of glycosylphosphatidylinositol (GPI)-linked molecules. The combination of CD157 and FLAER was used, since FLAER recognizes all GPI-linked molecules, while CD157 is absent on the membrane of eosinophils and expressed by neutrophils. Peripheral blood samples from normal subjects and patients with variable percentages of eosinophils (n = 31), and without any evidence for circulating immature myeloid cells, were stained with the combination of FLAER-Alexa Fluor and CD157-PE. A FascCanto II cytometer was used. Granulocytes were gated after CD33 staining and eosinophils were identified as CD157(-)/FLAER(+) events. Neutrophils were identified as CD157(+)/FLAER(+) events. The percentages of eosinophils detected by this method showed a very significant correlation both with automated counting and with manual counting (r = 0.981 and 0.989, respectively). Sorting assays were carried out by a S3 Cell Sorter: cytospins obtained from CD157(-)/FLAER(+) events consisted of 100% eosinophils, while samples from CD157(+)/FLAER(+) events were represented only by neutrophils. In conclusion, this method shows high sensitivity and specificity in order to distinguish eosinophils from neutrophils by flow cytometry. However, since CD157 is gradually up-regulated throughout bone marrow myeloid maturation, our method cannot be applied to cases characterized by immature myeloid cells.

Eosinophilic Esophagitis in Brazilian Pediatric Patients

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Mayra Isabel Correia Pinheiro

2013-01-01

Full Text Available We examined 11 pediatric patients with eosinophilic esophagitis with a tardy diagnosis. The symptoms were initially thought to be related to other diseases, leading to the use of inadequate therapeutic approaches. The patients were between 3 and 17 years old (mean 7.8 ± 3.8 years, and 8 of the patients were male. Common symptoms included abdominal pain, regurgitation, difficulty in gaining weight, vomiting, dysphagia, and coughing. The mean age for the onset of symptoms was 4.3 ± 2.9 years. Endoscopic findings included normal mucosa in five (45% patients, thickening of the mucosa with longitudinal grooves in three (27%, erosive esophagitis in two (18%, and a whitish stippling in one (9% patient. Treatment included the use of a topical corticosteroid for 10 patients. In eight (73% cases, the treatment made the symptoms disappear. Ten patients underwent histopathological management after treatment, with a decrease in the number of eosinophils.

Bone marrow contribution to eosinophilic inflammation

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Denburg Judah A

1997-01-01

Full Text Available Allergen-induced bone marrow responses are observable in human allergic asthmatics, involving specific increases in eosinophil-basophil progenitors (Eo/B-CFU, measured either by hemopoietic assays or by flow cytometric analyses of CD34-positive, IL-3Ralpha-positive, and/or IL-5-responsive cell populations. The results are consistent with the upregulation of an IL-5-sensitive population of progenitors in allergen-induced late phase asthmatic responses. Studies in vitro on the phenotype of developing eosinophils and basophils suggest that the early acquisition of IL-5Ralpha, as well as the capacity to produce cytokines such as GM-CSF and IL-5, are features of the differentiation process. These observations are consistent with findings in animal models, indicating that allergen-induced increases in bone marrow progenitor formation depend on hemopoietic factor(s released post-allergen. The possibility that there is constitutive marrow upregulation of eosinophilopoiesis in allergic airways disease is also an area for future investigation.

Allergen-Induced Increases in Interleukin-25 and Interleukin-25 Receptor Expression in Mature Eosinophils from Atopic Asthmatics.

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Tang, Wei; Smith, Steven G; Salter, Brittany; Oliveria, John Paul; Mitchell, Patrick; Nusca, Graeme M; Howie, Karen; Gauvreau, Gail M; O'Byrne, Paul M; Sehmi, Roma

2016-01-01

Interleukin (IL)-25 plays a pivotal role in type 2 immune responses. In a baseline cross-sectional study, we previously showed that IL-25 plasma levels and IL-25 receptor (IL-25R: IL-17RA, IL-17RB, and IL-17RA/RB) expression on mature blood eosinophils are increased in atopic asthmatics compared to normal nonatopic controls. This study investigated allergen-induced changes in IL-25 and IL-25R expression in eosinophils from asthmatics. Dual responder atopic asthmatics (n = 14) were enrolled in this randomized diluent-controlled crossover allergen challenge study. Blood was collected before and 24 h after the challenge. The surface expression of IL-25R was evaluated by flow cytometry on eosinophils and Th2 memory cells. In addition, plasma levels of IL-25 were measured by ELISA, and functional responses to IL-25 including type 2 cytokine expression, degranulation, and the migrational responsiveness of eosinophils were evaluated in vitro. Following the allergen but not the diluent inhalation challenge, significant increases in the expression of IL-17RB and IL-17RA/B were found on eosinophils but not on Th2 memory cells. IL-25 plasma levels and the number of eosinophils but not of Th2 memory cells expressing intracellular IL-25 increased significantly in response to the allergen but not the diluent challenge. Stimulation with physiologically relevant concentrations of IL-25 in vitro caused (i) degranulation of eosinophils (measured by eosinophil peroxidase release), (ii) enhanced intracellular expression of IL-5 and IL-13, and (iii) priming of eosinophil migration to eotaxin. IL-25 stimulated intracellular cytokine expression, and the migration of eosinophils was blocked in the presence of a neutralizing IL-25 antibody. Our findings suggest that the IL-25/IL-25R axis may play an important role in promoting the recruitment and proinflammatory function of eosinophils in allergic asthma. © 2016 S. Karger AG, Basel.

Antibody-secreting cells in respiratory tract tissues in the absence of eosinophils as supportive partners.

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Sealy, Robert E; Surman, Sherri L; Vogel, Peter; Hurwitz, Julia L

2016-11-01

Antibody-secreting cells (ASCs) in respiratory tract tissues provide a first line of defense against invading pathogens. These cells often secrete IgA that is efficiently transcytosed across epithelial barriers into the airway lumen where pathogens can be blocked at their point of entry. Previous literature has reported that in the bone marrow, eosinophils are required for the maintenance of ASCs, and that eosinophils co-localize with ASCs as nearest neighbors. To determine if these rules similarly apply to the maintenance of ASCs in respiratory tract tissues, we evaluated virus-specific responses 1 month and 4 months following an intranasal virus infection of eosinophil-null (∆dblGATA-1) mice. Results showed that ASCs were fractionally reduced, but were nonetheless observed in respiratory tract tissues in the absence of eosinophils. Virus-specific antibodies were similarly observed in the airways of eosinophil-deficient mice. Respiratory tract ASCs were also present in mice lacking neutrophils (Mcl1 ∆M ). The staining of tissue sections from the upper respiratory tract of wild-type mice following viral infections demonstrated that virus-specific ASCs were most frequently situated adjacent to epithelial cells rather than eosinophils or neutrophils. Taken together, these data emphasize that rules for cell maintenance are not absolute and that ASCs can survive in the respiratory tract without eosinophils or neutrophils as their nearest neighbors. © The Japanese Society for Immunology. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Characterization of inflammatory cell infiltration in feline allergic skin disease.

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Taglinger, K; Day, M J; Foster, A P

2007-11-01

Sixteen cats with allergic dermatitis and six control cats with no skin disease were examined. Lymphoid and histiocytic cells in skin sections were examined immunohistochemically and mast cells were identified by toluidine blue staining. The 16 allergic cats showed one or more of several features (alopecia, eosinophilic plaques or granulomas, papulocrusting lesions), and histopathological findings were diverse. In control cats there were no cells that expressed IgM or MAC387, a few that were immunolabelled for IgG, IgA or CD3, and moderate numbers of mast cells. In allergic cats, positively labelled inflammatory cells were generally more numerous in lesional than in non-lesional skin sections, and were particularly associated with the superficial dermis and perifollicular areas. There were low numbers of plasma cells expressing cytoplasmic immunoglobulin; moderate numbers of MHC II-, MAC387- and CD3-positive cells; and moderate to numerous mast cells. MHC class II expression was associated with inflammatory cells morphologically consistent with dermal dendritic cells and macrophages, and epidermal Langerhans cells. Dendritic cells expressing MHC class II were usually associated with an infiltrate of CD3 lymphocytes, suggesting that these cells participate in maintenance of the local immune response by presenting antigen to T lymphocytes. These findings confirm that feline allergic skin disease is characterized by infiltration of activated antigen-presenting cells and T lymphocytes in addition to increased numbers of dermal mast cells. This pattern mimics the dermal inflammation that occurs in the chronic phase of both canine and human atopic dermatitis.

Helminth antigens counteract a rapid high-fat diet-induced decrease in adipose tissue eosinophils.

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van den Berg, Susan M; van Dam, Andrea D; Kusters, Pascal J H; Beckers, Linda; den Toom, Myrthe; van der Velden, Saskia; Van den Bossche, Jan; van Die, Irma; Boon, Mariëtte R; Rensen, Patrick C N; Lutgens, Esther; de Winther, Menno P J

2017-10-01

Brown adipose tissue (BAT) activation and white adipose tissue (WAT) beiging can increase energy expenditure and have the potential to reduce obesity and associated diseases. The immune system is a potential target in mediating brown and beige adipocyte activation. Type 2 and anti-inflammatory immune cells contribute to metabolic homeostasis within lean WAT, with a prominent role for eosinophils and interleukin (IL)-4-induced anti-inflammatory macrophages. We determined eosinophil numbers in epididymal WAT (EpAT), subcutaneous WAT (ScAT) and BAT after 1 day, 3 days or 1 week of high-fat diet (HFD) feeding in C57Bl/6 mice. One day of HFD resulted in a rapid drop in eosinophil numbers in EpAT and BAT, and after 3 days, in ScAT. In an attempt to restore this HFD-induced drop in adipose tissue eosinophils, we treated 1-week HFD-fed mice with helminth antigens from Schistosoma mansoni or Trichuris suis and evaluated whether the well-known protective metabolic effects of helminth antigens involves BAT activation or beiging. Indeed, antigens of both helminth species induced high numbers of eosinophils in EpAT, but failed to induce beiging. In ScAT, Schistosoma mansoni antigens induced mild eosinophilia, which was accompanied by slightly more beiging. No effects were observed in BAT. To study type 2 responses on brown adipocytes directly, T37i cells were stimulated with IL-4. This increased Ucp1 expression and strongly induced the production of eosinophil chemoattractant CCL11 (+26-fold), revealing that brown adipocytes themselves can attract eosinophils. Our findings indicate that helminth antigen-induced eosinophilia fails to induce profound beiging of white adipocytes. © 2017 Society for Endocrinology.

Association of interleukin 1 receptor-like 1 gene polymorphisms with eosinophilic phenotype in Japanese adults with asthma.

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Inoue, Hideki; Ito, Isao; Niimi, Akio; Matsumoto, Hisako; Oguma, Tsuyoshi; Tajiri, Tomoko; Iwata, Toshiyuki; Nagasaki, Tadao; Kanemitsu, Yoshihiro; Morishima, Toshitaka; Hirota, Tomomitsu; Tamari, Mayumi; Wenzel, Sally E; Mishima, Michiaki

2017-11-01

IL1RL1 (ST2) is involved in Th2 inflammation including eosinophil activation. Single nucleotide polymorphisms (SNPs) of the IL1RL1 gene are associated with asthma development and increased peripheral blood eosinophil counts. However, the association between IL1RL1 SNPs and eosinophilic phenotype among adults with asthma remains unexplored. In a primary cohort of 110 adult Japanese patients with stable asthma, we examined the associations between IL1RL1 SNPs and clinical measurements including forced expiratory volume (FEV 1 ), airway reversibility of FEV 1 , exhaled nitric oxide (FeNO), serum soluble-ST2 (sST2) levels, peripheral blood eosinophil differentials and serum total IgE level. The findings in the primary cohort were confirmed in a validation cohort of 126 adult Japanese patients with stable asthma. Patients with minor alleles in 3 SNPs (rs17026974, rs1420101, and rs1921622) had high FeNO, blood eosinophil differentials, and reversibility of FEV 1 , but low levels of serum sST2 and FEV 1 . Minor alleles of rs1041973 were associated with low serum sST2 levels alone. In the validation cohort, minor alleles of rs1420101 were associated with high FeNO and blood eosinophil differentials, whereas minor alleles of rs17026974 and rs1921622 were associated with high blood eosinophil differentials and FeNO, respectively. Multivariate analyses revealed that the minor allele of rs1420101 additively contributed to the FeNO, blood eosinophil differentials, and reversibility of FEV 1 . The minor alleles of IL1RL1 SNPs were associated with high FeNO and peripheral blood eosinophilia among adult Japanese patients with stable asthma. IL1RL1 SNPs may characterize the eosinophilic phenotype with greater eosinophilic inflammation in the Japanese asthma cohort. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

The Pathophysiology of Eosinophilic Esophagitis

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Daniel Avi Lemberg

2014-05-01

Full Text Available Eosinophilic Esophagitis (EoE is an emerging disease characterised by esophageal eosinophilia (>15eos/hpf, lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with TGF-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE.

The distribution of blood eosinophil levels in a Japanese COPD clinical trial database and in the rest of the world

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Ishii, Takeo; Hizawa, Nobuyuki; Midwinter, Dawn; James, Mark; Hilton, Emma; Jones, Paul W

2018-01-01

Background Blood eosinophil measurements may help to guide physicians on the use of inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD). Emerging data suggest that COPD patients with higher blood eosinophil counts may be at higher risk of exacerbations and more likely to benefit from combined ICS/long-acting beta2-agonist (LABA) treatment than therapy with a LABA alone. This analysis describes the distribution of blood eosinophil count at baseline in Japanese COPD patients in comparison with non-Japanese COPD patients. Methods A post hoc analysis of eosinophil distribution by percentage and absolute cell count was performed across 12 Phase II–IV COPD clinical studies (seven Japanese studies [N=848 available absolute eosinophil counts] and five global studies [N=5,397 available eosinophil counts] that included 246 Japanese patients resident in Japan with available counts). Blood eosinophil distributions were assessed at baseline, before blinded treatment assignment. Findings Among Japanese patients, the median (interquartile range) absolute eosinophil count was 170 cells/mm3 (100–280 cells/mm3). Overall, 612/1,094 Japanese patients (56%) had an absolute eosinophil count ≥150 cells/mm3 and 902/1,304 Japanese patients (69%) had a percentage eosinophil ≥2%. Among non-Japanese patients, these values were 160 (100–250) cells/mm3, 2,842/5,151 patients (55%), and 2,937/5,155 patients (57%), respectively. The eosinophil distribution among Japanese patients was similar to that among non-Japanese patients. Within multi-country studies with similar inclusion criteria, the eosinophil count was numerically lower in Japanese compared with non-Japanese patients (median 120 vs 160 cells/mm3). Interpretation The eosinophil distribution in Japanese patients seems comparable to that of non-Japanese patients; although within multi-country studies, there was a slightly lower median eosinophil count for Japanese patients compared with

Human eosinophils modulate peripheral blood mononuclear cell response to Schistosoma mansoni adult worm antigen in vitro.

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Tweyongyere, R; Namanya, H; Naniima, P; Cose, S; Tukahebwa, E M; Elliott, A M; Dunne, D W; Wilson, S

2016-08-01

High numbers of eosinophils are observed in parasitic infections and allergic diseases, where they are proposed to be terminally differentiated effector cells that play beneficial role in host defence, or cause harmful inflammatory response. Eosinophils have been associated with killing of schistosomulae in vitro, but there is growing evidence that eosinophils can play additional immuno-regulatory role. Here, we report results of a study that examines peripheral blood mononuclear cell (PBMC) cytokine responses to Schistosoma mansoni adult worm antigen (SWA) when stimulated alone or enriched with autologous eosinophils. Production of the Th-2 type cytokines interleukin (IL)-4, IL-5 and IL-13 was lower (P = 0·017, 0·018 and eosinophil cultures than in PBMC-only cultures stimulated with SWA. Substantial levels of IL-13, IL-10, interferon gamma and tumour necrosis factor alpha were recorded in cultures of eosinophils, but none of these cytokines showed significant association with the observed eosinophil-induced drop in cytokine responses of PBMC. Transwell experiments suggested that the observed effect is due to soluble mediators that downmodulate production of Th-2 type cytokines. This study shows that eosinophils may down-modulate schistosome-specific Th-2 type cytokine responses in S. mansoni-infected individuals. The mechanism of this immune modulation remains to be elucidated. © 2016 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

Urinary Eosinophil Protein X in Childhood Asthma : Relation with Changes in Disease Control and Eosinophilic Airway Inflammation

NARCIS (Netherlands)

Nuijsink, Marianne; Hop, Wim C. J.; Sterk, Peter J.; Duiverman, Eric J.; De Jongste, Johan C.