Absence Of Eosinophils Research Articles

Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages

Eosinophils in visceral adipose tissue (VAT) have been implicated in metabolic homeostasis and the maintenance of alternatively activated macrophages (AAMs). The absence of eosinophils can lead to adiposity and systemic insulin resistance in experimental animals, but what maintains eosinophils in adipose tissue is unknown. We show that interleukin-5 (IL-5) deficiency profoundly impairs VAT eosinophil accumulation and results in increased adiposity and insulin resistance when animals are placed on a high-fat diet. Innate lymphoid type 2 cells (ILC2s) are resident in VAT and are the major source of IL-5 and IL-13, which promote the accumulation of eosinophils and AAM. Deletion of ILC2s causes significant reductions in VAT eosinophils and AAMs, and also impairs the expansion of VAT eosinophils after infection with Nippostrongylus brasiliensis, an intestinal parasite associated with increased adipose ILC2 cytokine production and enhanced insulin sensitivity. Further, IL-33, a cytokine previously shown to promote cytokine production by ILC2s, leads to rapid ILC2-dependent increases in VAT eosinophils and AAMs. Thus, ILC2s are resident in VAT and promote eosinophils and AAM implicated in metabolic homeostasis, and this axis is enhanced during Th2-associated immune stimulation.

Histopathology and correlates of systemic disease in adult Henoch-Schönlein purpura: A retrospective study of microscopic and clinical findings in 68 patients at Mayo Clinic

The histopathology of Henoch-Schönlein purpura (HSP) is well defined, but specific markers have not been correlated with systemic involvement. We sought to evaluate whether histopathologic markers were associated with renal or other systemic involvement in adult HSP. We retrospectively reviewed clinical information and pathology slides of 68 adult patients with HSP seen at Mayo Clinic between 1992 and 2011. Of the 68 patients, mean age was 45.8 years and 41 (60%) of the patients were male. Renal involvement was observed in 30 patients (44%), gastrointestinal tract in 27 (40%), joint in 32 (47%), and any systemic signs in 52 (76%). Patients who were older than 40 years and had leukocytoclastic vasculitis with an absence of eosinophils on skin biopsy specimen had higher rates of renal involvement than those who did not have both of these features (75% vs 27%; P < .001). Patients with skin biopsy specimens showing leukocytoclastic vasculitis and an absence of histiocytes had higher rates of gastrointestinal tract involvement (P = .03). Age of 40 years or younger was associated with increased risk for gastrointestinal tract involvement and a nonsignificant trend for joint involvement (P = .004 and P = .06, respectively). This study is retrospective, and the causative factors of HSP were unable to be determined in many patients. Patients older than 40 years with HSP who had an absence of eosinophils on skin biopsy specimen had a nearly 3-times increased risk of renal involvement compared with patients who did not have both features.

Strongyloidiasis

Strongyloides stercoralis is endemic to many tropical regions; however, there is limited knowledge concerning the clinical implication of this helminth, particularly in urban medical centers. We report a case series of strongyloidiasis in our urban medical center in New York City. Patients over the age of 18 years who were examined in our institution from January 1998 to May 2011 were identified by electronic medical record search using International Classification of Diseases, 9th Revision codes. We identified 22 cases of S. stercoralis. Eleven patients were men and 11 were women, with the average age at diagnosis being 62.4 years. Fourteen patients emigrated from the Caribbean, one from Nepal, five were blacks born in the USA, and two did not have their birthplace documented. The main presenting complaints were diarrhea (9/22), abdominal pain (6/22), vomiting (7/22), and weight loss (8/22). Seventeen patients demonstrated eosinophilia. Four patients were positive for human T-lymphotropic virus-1 antibodies, and three patients were infected with HIV. Diagnosis was made with stool examination (19/22), bronchoalveolar lavage (1/22), gastric biopsy (1/22), and duodenal biopsy (3/22). Among six patients who had upper endoscopy performed, the findings commonly included gastritis and gastric and duodenal ulcers. After treatment, 12/22 showed resolution of symptoms. Although a diagnostic approach tends to start with stool collections, consideration of upper endoscopy with biopsy in symptomatic patients is advisable. The absence of eosinophilia should not deter the clinician from seeking a diagnosis. Although often not done, ascertaining HIV and human T-lymphotropic virus-1 status should be part of the work-up.

Eosinophils Contribute to IL-4 Production and Shape the T-Helper Cytokine Profile and Inflammatory Response in Pulmonary Cryptococcosis

Susceptibility to infection with Cryptococcus neoformans is tightly determined by production of IL-4. In this study, we investigated the time course of IL-4 production and its innate cellular source in mice infected intranasally with C. neoformans. We show that pulmonary IL-4 production starts surprisingly late after 6 weeks of infection. Interestingly, in the lungs of infected mice, pulmonary T helper (Th) cells and eosinophils produce significant amounts of IL-4. In eosinophil-deficient ΔdblGATA mice, IL-33 receptor-expressing Th2s are significantly reduced, albeit not absent, whereas protective Th1 and Th17 responses are enhanced. In addition, recruitment of pulmonary inflammatory cells during infection with C. neoformans is reduced in the absence of eosinophils. These data expand previous findings emphasizing an exclusively destructive effector function by eosinophilic granulocytes. Moreover, in ΔdblGATA mice, fungal control is slightly enhanced in the lung; however, dissemination of Cryptococcus is not prevented. Therefore, eosinophils play an immunoregulatory role that contributes to Th2-dependent susceptibility in allergic inflammation during bronchopulmonary mycosis.

Eosinophils Are Dispensable for Allergic Remodeling and Immunity in a Model of House Dust Mite–induced Airway Disease

Current thinking accredits eosinophils with preeminent contributions to allergic airway responses, including a major role in the development of airway remodeling, a process thought to significantly contribute to airway dysfunction. However, direct evidence in support of this notion is limited and often controversial. We elucidated the requirement for eosinophils in the generation of allergic sensitization, airway inflammation, and remodeling in a model involving chronic respiratory exposure to house dust mite (HDM). We used three methods to selectively eliminate eosinophils, a depleting antibody (anti-CCR3), and two strains of eosinophil-deficient mice (ΔdblGATA and the transgenic line PHIL). Anti-CCR3 treatment markedly reduced pulmonary eosinophilia (> 80%) over the course of HDM exposure but had no effect on the remaining inflammatory response, the extent of lung Th2 cells, or the development of remodeling-associated changes, including subepithelial collagen deposition and smooth muscle thickening. In addition, we observed that, despite the absence of eosinophils, HDM-exposed GATA mice mounted robust airway and lung inflammation and hyperresponsiveness and showed a remodeling response equivalent to that observed in wild-type mice. Moreover, these mice had similar serum HDM-specific IgE levels and Th2-associated splenocyte cytokine production as HDM-exposed wild-type control mice. Similar observations were made in PHIL eosinophil-deficient mice subjected to chronic HDM exposure, although slight decreases in airway mononuclear cells, but not lung Th2 cells, and remodeling were noted. Collectively, these data demonstrate that, at variance with the prevailing paradigm, eosinophils play negligible roles in the generation of HDM-induced allergic immunity and airway remodeling.

A Case of del(16)(q22) in a Patient with Acute Myeloid Leukemia with Complex Karyotype

Inversion of chromosome 16 [inv(16)(p13.1q22)] and t(16;16)(p13.1;q22) are associated with acute myelomonocytic leukemia (AMML) with eosinophilia and a favorable prognosis. On the other hand, patients with del(16)(q22) usually present with MDS or chronic myelomonocytic leukemia (CMML), which can evolve to AMML without eosinophilia, and this chromosomal aberration is associated with older age, a complex karyotype, and a poor prognosis. We report a case of AML with del(16)(q22) which showed a complex karyotype, absence of eosinophilia in bone marrow study and a poor response to chemotherapy.

Drug allergy

Drug allergy is one type of adverse reaction to drugs and encompasses a spectrum of hypersensitivity reactions with heterogeneous mechanisms and clinical presentations. A thorough history is essential to the management of drug allergy. Laboratory testing has a very limited role in the management of drug allergy. Graded dose challenges and procedures to induce drug tolerance might be required in patients with drug allergy when there is a definite need for a particular agent. Management of reactions to specific agents, including beta-lactam antibiotics, sulfonamides, local anesthetics, radiocontrast media, angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, and biologic modifiers, will be discussed in further detail.

Effects of steroid therapy on inflammatory cell subtypes in asthma

RationaleAirway inflammation in asthma is heterogeneous with different phenotypes. The inflammatory cell phenotype is modified by corticosteroids and smoking. Steroid therapy is beneficial in eosinophilic asthma (EA), but evidence is...

Fulminant colitis and toxic myocarditis: a unifying cause?

In June, 2006, a 44-year-old previously healthy woman from a poor socio-economic background presented to us with a 5-day history of fever, dyspnoea, tight chest pain, and postural dizziness. This was preceded by an episode of diarrhoea over a week. On admission, respiratory rate was 40 breaths per min, radial pulse was regular at 130 beats per min, and blood pressure was 80/50 mm Hg. She had central cyanosis, was sweating profusely, and had cold peripheries. Heart sounds showed triple rhythm and she had fi ne basal crepitations in her lungs. Her abdomen was soft and non-tender; there was no sign of hepatosplenomagaly or ascites. She was promptly resuscitated with intravenous fl uids, but required intubation and mechanical ventilation in the intensive care unit. Broad-spectrum antibiotics including benzylpenicillin and ceftriaxone were given. Hypotension and tachycardia persisted despite maximum inotropic support. She subsequently developed acute renal failure and severe hepatic dysfunction; peritoneal dialysis and liver failure regimen were started. A 12-lead ECG showed ST segment depressions in leads I, aVL, and V2 to V6. Troponin T concentration was high. Initial echocardiography showed dilatation of all cardiac chambers and a hypokinetic left ventricle with left ventricular ejection fraction 42%; the latter declined to 36% on day 3. C-reactive protein was high (>1000 mg/L). White blood cell count was 10·8×109/L (76% neutrophils; 20% lymphocytes; 4% eosinophils). Blood and peritoneal fl uid cultures were repeatedly negative. No antibodies to the following were detectable: dengue virus, coxackievirus, infl uenza A and B viruses, parainfl uenza virus, adenovirus, RSV, hanta virus, herpes virus, HIV. Tests for leptospirosis were also negative. She had a generalised tonic-clonic convulsion on day 7; EEG showed generalised slow waves. The seizures were managed, but she died on day 15. At autopsy, purulent ascitic fl uid and organised pus on serosal surfaces were found. The caecum had multiple transverse ulcers and a perforation in the lateral wall. The heart was dilated, and the myocardium was fl abby and weighed 0·2 kg. There was a thin layer of pericardial eff usion. Staining of the myocardium for gram-negative bacteria and eosinophils was negative. However, fl orid colitis with Entamoeba histolytica in abundance was detected in the caecum, which also showed many fl ask-shaped ulcers, some of which had penetrated up to the serosa. The ulcer base and the adjacent caecal wall showed multiple amoebae with ingested red blood cells. Amoebae were also noted to be invading the muscular propria and the subserosal surface (fi gure A). However, molecular identifi cation was not done because of limited available resources. There were several foci of myocardial necrosis, some of which were organised with little infl ammation, suggestive of toxic myocarditis (fi gure B). A viral aetiology was initially considered because it is the most common cause of myocarditis. The possibility of an amoebic cause was not entertained antemortem, but the autopsy fi ndings confi rmed toxic cardiomyopathy. The absence of eosinophils and gramnegative bacteria in the myocardium supports the possible amoebic aetiology secondary/concurrent to bowel pathology. Pre-existing heart failure was unlikely because the patient was in good health just before the illness. E histolytica is primarily a bowel pathogen that causes colitis and liver abscesses. Rarely it causes mening oencephalitis and pericarditis. There are about 50 million cases of amoebiasis in the world and nearly 100 000 people die annually from complications. The case fatality rate remains high at 29% in some parts of Asia; the case fatality rate in Sri Lanka is 0·6/100 000 per year. Although E histolytica has been implicated in cases of dilated cardiomyopathy in animals, it has not been reported in human beings. Our case shows an uncommon consequence of a relatively common disease.

CYTOLOGICAL PECULIARITIES OF LOCAL WOUNDS IN DIFFERENT PHASES OF THE REPARATIVE PROCESS

The cytogramms of 57 patients with local wounds were investigated It is shown that cytological composition of wound bioptate is different in dependence on duration of its existence and corresponds to reparative process phases. In the patients with complication postoperative period of autodermoplastic, unlike the patients with total vitality of dermal shred, the initial condition of the cytogramm is characterized by absence of eosinophils and higher contents of degenerative forms of neirtophils.

The role of peripheral blood, bone marrow aspirate and especially bone marrow trephine biopsy in distinguishing atypical chronic myeloid leukemia from chronic granulocytic leukemia and chronic myelomonocytic leukemia

To better realize the features of peripheral blood (PB), bone marrow (BM) aspirate and especially BM trephine biopsy in atypical chronic myeloid leukemia (aCML). We studied PB, BM smears in 35 cases of aCML and compared with 84 cases of chronic granulocytic leukemia chronic phase (CGL-CP), 39 cases of chronic myelomonocytic leukemia (CMML). In addition, we evaluated characteristics of BM trephine biopsies in 21 cases of aCML and compared with 68 cases of CGL-CP, 20 cases of CMML. All aCML patients presented with leukocytosis (median WBC 17.3 x 10(9)/L), 48% had moderate anemia, and 85% had thrombocytopenia. Values of monocytes, eosinophils, basophils, percentage of immature granulocytes and monocytes (0.63 +/- 0.41 x 10(9)/L, 0.18 +/- 0.16 x 10(9)/L, 0.09 +/-0.08 x 10(9)/L, 6.27 +/- 3.09%, and 2.46 +/- 1.75%, respectively) were useful in distinguishing aCML from CGL-CP and CMML groups. The BM smears showed that striking dysgranulopoieis (100%), dyserythropoiesis (48.6%), percentage of blasts, nucleated erythrocytes, monocytes, eosinophils, and basophils (2.45 +/- 2.06%, 7.76 +/- 2.89%, 1.30 +/- 1.21%, 1.47 +/- 1.60%, and 1.15 +/- 1.08%, respectively) were all important parameters for a diagnosis of aCML. On BM trephine sections, aCML was characterized as hypercellularity, a moderate degree of reticulin fibrosis (71.4%), lymphocytopenia (76.2%), plasmacytopenia (90.5%), abnormal localization of immature precursors (28.5%), and absence of eosinophilia, basophilia, monocytosis. Furthermore, BM imprints, immunohistochemical, and cytochemical staining findings provided important morphological reference to BM trephine sections and made the identification of nucleated cells more convenient. Besides the findings observed in PB and BM aspirate, features of BM trephine biopsy (including BM trephine section, BM imprint, immunohistochemical, and cytochemical staining) can also aid in the diagnosis of aCML.

Eosinophil Deficiency Compromises Parasite Survival in Chronic Nematode Infection

Immune responses elicited by parasitic worms share many features with those of chronic allergy. Eosinophils contribute to the inflammation that occurs in both types of disease, and helminths can be damaged or killed by toxic products released by eosinophils in vitro. Such observations inform the widely held view that eosinophils protect the host against parasitic worms. The mouse is a natural host for Trichinella spiralis, a worm that establishes chronic infection in skeletal muscle. We tested the influence of eosinophils on T. spiralis infection in two mouse strains in which the eosinophil lineage is ablated. Eosinophils were prominent in infiltrates surrounding infected muscle cells of wild-type mice; however, in the absence of eosinophils T. spiralis muscle larvae died in large numbers. Parasite death correlated with enhanced IFN-gamma and decreased IL-4 production. Larval survival improved when mice were treated with inhibitors of inducible NO synthase, implicating the NO pathway in parasite clearance. Thus, the long-standing paradigm of eosinophil toxicity in nematode infection requires reevaluation, as our results suggest that eosinophils may influence the immune response in a manner that would sustain chronic infection and insure worm survival in the host population. Such a mechanism may be deployed by other parasitic worms that depend upon chronic infection for survival.

Analysis of IL-10, IL-4 and TNF-α polymorphisms in drug-induced liver injury (DILI) and its outcome

The aim of this study was to assess whether genetic polymorphism of three important candidate cytokine genes, IL-10 (-1082G/A, -819C/T, and -592C/A), IL-4 (-590C/T) and TNF-alpha (-308G/A), play a role in the susceptibility to developing drug-induced liver injury (DILI), and in determining its phenotypic expression and severity. Cytokine genotyping was analysed using TaqMan 5' allelic discrimination assay in 140 DILI patients (mean age 51 y, range 13-82, with equal sex distribution) included in the Spanish Registry and 268 healthy controls. Genotypes, haplotypes and allele frequencies were similar for both cases and controls. The low IL-10 producing haplotype was more prevalent in DILI patients with the absence of peripheral blood eosinophilia (Pc=0.004, OR=5.29, 95% CI: 2.04-13.67), revealing significantly lower median eosinophil counts (0.19 x 10(9)L; P<0.0002) compared to the intermediate (0.24 x 10(9)L) and high (0.40 x 10(9)L) IL-10 haplotypes. All cases with serious DILI outcome carried low or intermediate IL-10 producing haplotype and had normal or low eosinophil counts. IL-10, IL-4 and TNF-alpha genetic polymorphisms were not related to the risk of developing DILI. Low IL-10 producing haplotype is associated with low eosinophil count, absence of eosinophilia and may be associated with worse clinical outcome from DILI.

Bone marrow trephine morphology and immunohistochemical findings in chronic myelomonocytic leukaemia

Chronic myelomonocytic leukaemia (CMML) is a clonal disorder with myelodysplastic/myeloproliferative features. Its diagnosis is based on the presence of peripheral blood monocytosis and bone marrow aspirate findings, according to World Health Organization criteria. However, bone marrow trephine biopsy (BMTB) features characteristic of CMML have not been adequately investigated. We studied BMTB in 20 cases of CMML-1 and three cases of CMML-2 and compared with ten cases of polycythaemia vera, ten cases of chronic myeloid leukaemia (chronic phase) and ten cases of florid myeloid hyperplasia (MH). Furthermore, we evaluated the use of CD34, CD117 and CD68 (PGM-1) antibodies in diagnosis and subtyping of CMML and in differentiating from other categories. Hypercellularity, high myeloid:erythroid ratio, increased proportion of 'myelo/monocytic' cells often seen as clusters and/or nodules, absence of eosinophilia, and presence of abnormal localisation of immature precursors (ALIP) and dysmegakaryopoiesis can aid in the diagnosis of CMML in BMTB. CD68 (PGM-1) positive cells amounted to 20.7 +/- 6.1% cells among CMML trephines. The proportion of CD34(+) cells among cases of CMML-1 was </=5% and among CMML-2 was >/=10% cells in two of three cases and 5% in the other case. Morphological and immunohistochemical features of BMTB samples are extremely helpful in the diagnosis of CMML.

Is Eosinophil Dependence of Pulmonary Allergic Inflammation in Mice Really Strain Specific?

Pulmonary eosinophilia is a hallmark of atopic asthma and a common feature of mouse models of allergic inflammation. Different mouse strains have different sensitivity to allergens, different severity of Th2 driven inflammatory responses, and hence different degrees of induced pulmonary pathology. Indeed, many investigators have hypothesized that strain-specific differences (i.e. C57BL/6J vs. BALB/cJ) exist with regards to the utility of established allergen sensitization/challenge models. Moreover the role/contribution of eosinophils to allergen-induced pulmonary pathologies remains unresolved with suggestions that the importance of these activities may also be strain specific. We compared ovalbumin induced pulmonary allergic inflammation in eosinophil deficient mice (PHIL) on two genetic backgrounds, C57BL/6J and BALB/cJ. Lung histopathology and lung function were assessed. Our data demonstrate that the genetic ablation of eosinophils in PHIL mice occurs in both C57BL/6J vs. BALB/cJ. More importantly, irrespective of background strain the loss of eosinophils resulted in the attenuation of key allergen-induced lung pathologies. In particular, both strains of mice displayed a significant decrease in allergen-induced goblet cell metaplasia and the loss of AHR in the absence of eosinophils. Observed strain differences in terms of allergen-induced pathologies cannot be explained on the basis of strain-specific eosinophil effector functions.

Eosinophil-induced prognosis improvement of solid tumors could be enabled by their vesicle-mediated barrier permeability induction

Eosinophils are multifunctional cells, which contain and produce many biologically active substances. Generally, eosinophilia is associated with parasitic infections or allergic disorders, while according to recent studies eosinophil infiltration is also present in target tissues of both physiological and pathological processes, such as angiogenesis, embryogenesis, immune regulation, different infections or neoplasies, leading to tissue damage or remodeling. Reflecting on prognosis improvement in the case of solid tumors after eosinophilic infiltration of their capsules, it could be hypothesized that eosinophils are not tumoricidal per se; rather they can perforate such barriers through their vesicles' content, whereas the tumoricidal cytokines such as interleukin 4 (IL-4) fulfill the tumoral necrosis. This scenario can be supported by the fact that IL-4 originated from macrophages and lymphocytes fails to mediate tumor necrosis in vitro conditions in absence of eosinophils. In addition, the requirement of eosinophil-mediated increasing permeability among diverse biologic barriers and tissues may explain the eosinophils' introduction in capsules of cysts, mucosal membrane of respiratory and gastroenteric systems, hemato-encephalic barrier, in embryos, as well as in bacterial and parasitic membranes. Thus, in some situations rather than being multifunctional effectors per se, eosinophils, due to induction of target barrier dysfunction, may assure the host-required action, mediated by various kinds of leucocytes and their biologic effectors. Consequently, a better understanding of physiology and patho-physiology of this enigmatic cell will lead to new clinical strategies.

Blood eosinophilia as a marker of favorable outcome after allogeneic stem cell transplantation

Eosinophilia is observed in a variety of disorders including acute and chronic graft-versus-host disease (GVHD). The clinical records of 237 patients who underwent allogeneic stem cell transplantation (allo-SCT) were retrospectively reviewed. Eosinophilia, defined as a relative eosinophil count>4% within the first 100 days, was observed in 135 patients (57%). The incidence of grades II-IV acute GVHD was significantly higher in patients without eosinophilia than in those with eosinophilia (68% vs. 43%; P<0.001). The incidence of chronic GVHD was significantly higher in patients without eosinophilia than in those with eosinophilia (73% vs. 56%; P=0.011). Relapse rate was similar between patients with and without eosinophilia (33% vs. 27%; P=0.438). The probability of nonrelapse mortality was 10% in patients with eosinophilia, which was significantly lower than that in patients without eosinophilia (31%; P<0.001), and the overall survival (OS) at 3 years was 67% in patients with eosinophilia, which was significantly higher than that in patients without eosinophilia (51%; P=0.003). Multivariate analysis identified older age, high-risk disease, acute GVHD, sex disparity between patient and donor, and the absence of eosinophilia as significant factors for reduced OS. These data lead us to conclude that eosinophilia after allo-SCT may serve as a favorable prognostic marker.

Eosinophils Do Not Enhance the Trans-Basement Membrane Migration of Neutrophils

Background: There is increasing evidence that both neutrophilic and eosinophilic inflammation persist in the airways of patients with severe asthma. We have reported a positive relationship between the concentrations of eosinophils and neutrophils in sputum from severe asthmatics, suggesting a possible role of eosinophils in regulating neutrophilic inflammation. The aim of this study was to investigate whether activated eosinophils modify the trans-basement membrane migration (TBM) of neutrophils. Methods: Eosinophils and neutrophils were isolated from peripheral blood drawn from healthy donors. The TBM of neutrophils in response to a variety of chemoattractants was evaluated in the presence or absence of eosinophils by using the chambers with a Matrigel®-coated Transwell® insert. Results: As expected, eotaxin (10 nM) and RANTES (10 nM), but not IL-8 (10 nM), induced the TBM of eosinophils. On the contrary, only IL-8 induced the TBM of neutrophils. When eosinophils were coincubated with neutrophils and stimulated with IL-8, the TBM of eosinophils was significantly augmented. On the other hand, when neutrophils were coincubated with eosinophils and stimulated with eotaxin or RANTES, the TBM of neutrophils was not modified. Conclusions: Neutrophils migrated by IL-8 may lead eosinophils to accumulate in the airways of patients with severe asthma. On the other hand, it is unlikely that eosinophils migrated by chemoattractants such as CC chemokines regulate neutrophilic inflammation.

Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma

Background:Non-eosinophilic asthma is a potentially important clinicopathological phenotype since there is evidence that it responds poorly to inhaled corticosteroid therapy. However, little is known about the underlying airway immunopathology and...

Prostaglandin D2 Induces Chemotaxis in Eosinophils Via Its Receptor CRTH2 and Eosinophils May Cause Severe Ocular Inflammation in Patients With Allergic Conjunctivitis

Eosinophils are known to have important roles in the pathogenesis of allergic conjunctivitis. Prostaglandin (PG) D2, which has been implicated as a factor in allergic diseases, is known to have chemotactic activity for eosinophils. Its receptor, chemoattractant receptor homologous molecule expressed on TH2 (CRTH2), serves as a receptor for PGD2 and has been reported to mediate PGD2-dependent migration of eosinophils. In the present study, both eosinophil toxic activity for corneal epithelial cells and chemotaxis induced by PGD2 in normal volunteers were investigated. Expression of CRTH2 in normal subjects was also measured. Primary cultured corneal epithelial cells and eosinophils in serum from normal volunteers were used and a human corneal epithelial cell line was established. Studies were performed with/without amniotic membrane. CRTH2 expression on eosinophils was assessed by flow cytometry. Chemotaxis experiments were performed using a modified Boyden chamber technique. Corneal epithelial cells cultured with eosinophils showed higher floating epithelial cells and epithelial defect than those cultured in the absence of eosinophils. Flow cytometry analysis revealed that eosinophils expressed CRTH2. PGD2 induced chemotaxis of eosinophils. Corneal epithelial damage might be caused by eosinophils, which are recruited by PGD2 secretion via CRTH2 expressed on eosinophils.