Role Of Eosinophils Research Articles

Eosinophilic Bronchitis, Eosinophilia Associated Genetic Variants, and Notch Signaling in Asthma

While much has indeed been learned about the biology and role of eosinophils, the paradigm of eosinophils has the pros and cons in development of asthma. To answer the questions in the black box, this review firstly discusses the biological and morphological differences between asthma and eosinophilic bronchitis (EB). EB is an interesting clinical manifestation of eosinophilic airway disease that does not involve airway hyperresponsiveness (AHR), demonstrating that airway eosinophilia alone is insufficient to merit a diagnosis of asthma. Secondly, I will describe and discuss the effect(s) of single-nucleotide polymorphisms (SNPs) in the genes CCR3, IL-5 RECEPTOR ALPHA (IL5RA), and IL1RL1, and finally the in vitro and in vivo effects of Notch inhibition on both eosinophil differentiation and experimental asthma. Eosinophilic airway inflammation is not as important in the pathogenesis and maintenance of asthma as had previously been thought. However, the role of eosinophils in other asthma subphenotypes, including refractory or severely remodeled asthma, needs to be evaluated further. High-throughput methodologies such as genomics will facilitate the discovery of new markers of inflammation; these, in turn, will aid in the evaluation of the role of eosinophils in asthma and its various subphenotypes.

Analysis on the cause of eosinophilia in a neonatal intensive care unit

Purpose : Although eosinophilia is a common laboratory finding in many neonatal intensive care units (ICUs), its causative mechanisms remain obscure. We aimed to determine the causes of eosinophilia in the neonatal ICU environment. Methods : Serial eosinophil counts were determined weekly for 288 hospitalized, appropriately grown neonates. Infants were divided into four groups according to gestational age, and the incidence and etiologic factors of eosinophilia were retrospectively studied. Results : Absolute eosinophilia (>700/mm 3 ) was documented in 18% (52/288) of neonates. Twenty-two infants (42.3%) exhibited mild eosinophilia (700-999 cells/mm 3 ), 27 (51.9%) exhibited moderate eosinophilia (1,000-2,999 cells/mm 3 ), and 3 (5.8%) exhibited severe eosinophilia (>3,000 cells/mm 3 ). Of the 288 infants studied, 54 suffered sepsis. Thirty of these 54 infants (55.6%) showed eosinophilia, and 22 out of the remaining 234 infants (9%) without sepsis showed eosino- philia, indicating that eosinophilia was more prevalent in the sepsis group (P <0.05). All 5 infants suffering from broncho- pulmonary dysplasia showed eosinophilia, and 47 out of the remaining 283 infants (16.7%) without bronchopulmonary dysplasia showed eosinophilia. Thus, eosinophilia was more prevalent in the bronchopulmonary dysplasia group (P <0.05). Furthermore, increased prevalence of eosinophilia was associated with respiratory distress syndrome, ventilator use, blood transfusion, and total parenteral nutrition (P <0.05). Conclusion : Our results suggest that eosinophilia is influenced by sepsis and bronchopulmonary dysplasia, although it can also occur idiopathically at birth. Moreover, the potential role of eosinophils in conditions such as wound healing and fibrosis in sepsis or chronic lung disease may be a cause of eosinophilia. (Korean J Pediatr 2010;53:28-32)

Role of Eosinophil Cationic Protein in Asthma and Confounding Factors.

Role of Eosinophil Cationic Protein in Asthma and Confounding Factors.

Rethinking the Pathogenesis of Asthma

Asthma research has focused primarily on allergic pathways on the basis that the majority of asthma is associated with atopy, the recruitment of the Th2-type T cell, the cytokines, and the chemokines that are released on exposure to allergens, and the IgE pathway. However, despite considerable investment by industry, targeting these pathways has not resulted in new treatments being developed beyond blockade of cysteinyl leukotrienes and IgE and improvements in inhaled corticosteroids and beta(2)-adrenoceptor bronchodilators. Increasingly, it is recognized that asthma is a heterogeneous disorder, and while important, allergen sensitization is only one component of the disease, with many other environmental and genetic factors playing a role. In addition, these factors act locally on a susceptible airway epithelium that is both structurally and functionally deficient. It may be worthwhile to focus on increasing the resilience of the airways to environmental insults in addition to improving strategies that modify adaptive immunity or suppress inflammation.

S1883 To Biopsy or Not to Biopsy in Chronic Constipation? a Possible Role for Eosinophils in This Irritating Condition

S1883 To Biopsy or Not to Biopsy in Chronic Constipation? a Possible Role for Eosinophils in This Irritating Condition

Eosinophil Regulatory Activity in Models of Virus-Induced Inflammation

RATIONALE: Airway eosinophilia is a predictor of asthma exacerbations and a marker of asthma severity. Viral infections, including rhinovirus, account for the majority of asthma exacerbations. The role of eosinophils (EOS) in virus-induced inflammation remains to be defined. We chose to study human EOS regulatory activity in altering host responses to virus stimulation through interactions with peripheral blood mononuclear cells (PBMCs), monocytes, and epithelial cells (ECs). We have previously shown significant increases in IL-13 and IFN-gamma in co-culture experiments of EOS with CD4 + T-cells.

IL8 Requlation and Role of Eosinophils

IL8 Requlation and Role of Eosinophils

Churg-Strauss syndrome: 2005–2008 update

Churg-Strauss syndrome (CSS) is a rare necrotizing small-vessel vasculitis associated with eosinophil-rich granulomatous inflammation of tissues and vessels and is also associated with asthma and eosinophilia. Epidemiologic studies continue to show that CSS is the rarest of the necrotizing small-vessel vasculitides. However, it is not possible to know with any certainty if there has been an increase in incidence. There has been an attempt to divide the patients with CSS into an antineutrophil cytoplasmic antibody-positive and cytoplasmic antibody-negative group. The former group has an increased frequency of renal involvement, parenchymal pulmonary disease, constitutional symptoms, and peripheral and central nervous system involvement, whereas the latter group has more frequent cardiac disease. The role of eosinophils and antineutrophil cytoplasmic antibodies remains poorly defined but provocative. Leukotriene receptor antagonists do not appear to induce CSS but facilitate the tapering of glucocorticoids, which unmasks the condition. Glucocorticoids and cyclophosphamide remain the foundation of treatment for vasculitis, but there are other promising and less toxic alternatives on the horizon.

Activation of blood coagulation in bullous pemphigoid: role of eosinophils, and local and systemic implications

Bullous pemphigoid (BP) is a blistering skin disease caused by autoantibodies to hemidesmosomal proteins, with eosinophils participating in blister formation. Eosinophils are a source of tissue factor (TF), an initiator of blood coagulation. To evaluate the local and systemic activation of coagulation in BP. We studied 20 patients with active BP (eight re-evaluated during remission) and 40 controls. The coagulation markers prothrombin fragment F1+2 and d-dimer were measured in the plasma of all subjects and in both plasma and blister fluid of patients with BP. TF was evaluated immunohistochemically in skin specimens from the 20 patients and in 20 normal samples. F1+2 and d-dimer levels were higher in plasma of patients with BP (649 +/- 96 pmol L(-1) and 18.52 +/- 3.44 nmol L(-1), respectively) than in plasma of controls (157 +/- 7 pmol L(-1) and 1.42 +/- 0.06 nmol L(-1); P = 0.0001), and were very high in blister fluid (40 449 +/- 3491 pmol L(-1) and 1532.32 +/- 262.81 nmol L(-1); P = 0.0001). Plasma and blister fluid F1+2 and d-dimer levels paralleled blood and tissue eosinophilia and disease severity. In the eight patients re-evaluated during remission, there was a marked reduction in F1+2 (from 1127 +/- 144 to 287 +/- 52 pmol L(-1); P = 0.005) and d-dimer (from 24.03 +/- 4.08 to 4.69 +/- 1.51 nmol L(-1); P = 0.029). Immunohistochemistry revealed strong TF reactivity in BP skin (P = 0.0001), and colocalization studies confirmed eosinophils as a source of TF. The coagulation cascade is activated in BP and correlates with the severity of the disease and with eosinophilia, indicating that eosinophils play a role in coagulation activation via TF. The hypercoagulability may contribute to inflammation, tissue damage, blister formation and possibly thrombotic risk in BP.

Eosinophils: Biological Properties and Role in Health and Disease

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of diverse inflammatory responses, as well as modulators of innate and adaptive immunity. In this review, the biology of eosinophils is summarized, focusing on transcriptional regulation of eosinophil differentiation, characterization of the growing properties of eosinophil granule proteins, surface proteins and pleiotropic mediators, and molecular mechanisms of eosinophil degranulation. New views on the role of eosinophils in homeostatic function are examined, including developmental biology and innate and adaptive immunity (as well as their interaction with mast cells and T cells) and their proposed role in disease processes including infections, asthma, and gastrointestinal disorders. Finally, strategies for targeted therapeutic intervention in eosinophil-mediated mucosal diseases are conceptualized.

Structure-Based Rationale for Interleukin 5 Receptor Antagonism

Human interleukin 5 (IL5) is the major hematopoietin that stimulates the proliferation, migration and activation of eosinophils and is implicated in the pathogenesis of inflammatory and other myeloproliferative diseases. IL5 functions through the signaling of a common receptor subunit beta (beta c), in a receptor activation process that requires initial recruitment of an IL5 specific receptor subunit alpha (IL5Ralpha), for cytokine presentation to beta c. Important advances have been made to understand molecular mechanisms of cytokine recognition and receptor antagonism. Mutational studies indicate that a pair of charge complementary regions play an essential role in specific interaction between IL5Ralpha and IL5. Moreover, peptide studies with the IL5 system have identified a cyclic peptide inhibitor, AF17121, which binds specifically to IL5Ralpha by mimicking the cytokine. A key receptor-recognition pharmacophore has been identified in this peptide inhibitor, and sites of inhibitor recognition can be proposed in the homology-deduced structural model of IL5Ralpha. These results provide an experimental platform to derive enhanced-potency peptidomimetic inhibitors. Such inhibitors have potential use as tools to evaluate the role of eosinophilia in disease and as potential leads to antagonists to treat hyper-eosinophilic diseases such as eosinophilic esophagitis, asthma and chronic myeloproliferative leukemias.

Combating the Eosinophil with Anti–Interleukin-5 Therapy

The role of eosinophils in common diseases — such as asthma, parasitic disease, or allergic reactions — remains speculative. Even more puzzling is the eclectic group of rare disorders that constitute the hypereosinophilic syndromes. These syndromes are characterized by persistently high levels of blood eosinophils and their toxic mediators (e.g., eosinophilic cationic protein and eosinophil-derived neurotoxin), accompanied by severe multiorgan damage.1 The hypereosinophilic syndromes exclude secondary causes of eosinophilia such as infection while including myeloproliferative and lymphoproliferative variants, associated eosinophilic conditions that fulfill specific diagnostic criteria (e.g., the Churg–Strauss syndrome and mastocytosis), and the complex, undefined conditions affecting a large . . .

Eosinophils Induce Accumulation of Effector T Cells in Models of Allergic Pulmonary Inflammation

BackgroundEosinophil infiltration into the lung and airways is a hallmark of allergic asthma, yet the role of eosinophils in immune regulation of Th2-mediated pulmonary inflammation is poorly defined. Our data suggest a novel role for eosinophils as immune modulators that drive Th2-mediated pulmonary pathologies through activation/recruitment of Tcells and modulation of Th2 cytokines.MethodsTwo independent models of acute allergic inflammation were conducted in mice congenitally devoid of eosinophils (transgenic line: PHIL) and wild type mice. Mice were either sensitized and challenged with ovalbumin (OVA) or adoptively transferred with OVA-specific (OT-II) Th2 polarized T cells and eosinophils followed by challenge with OVA.ResultsPHIL mice that underwent the OVA sensitization/challenge had reduced bronchoalveolar lavage (BAL) levels of Th2 cytokines and reduced pulmonary T cell numbers as compared to wild type mice. Adoptive cell transfer studies using Th2 polarized OT-II T cells and eosinophils demonstrated that only adoptive transfer of both eosinophils and T cells increased BAL Th2 cytokines levels and accumulation of effector T cells (CD62L(-)CD44(+)) in the lungs of allergen-challenged mice.ConclusionsEosinophil effector functions in pulmonary Th2 inflammation likely includes not only destructive effector functions, but also immune regulating roles. The data suggest eosinophils contribute to Th2 inflammation through direct and indirect modulation of Th2 cytokines. More importantly, eosinophils appear to enhance Th2 inflammation through the activation/recruitment of T cells to the lymph nodes and lungs of allergen sensitized/challenged mice, which in turn implicates an expanded role for eosinophils in the onset and maintenance of allergic asthma. BackgroundEosinophil infiltration into the lung and airways is a hallmark of allergic asthma, yet the role of eosinophils in immune regulation of Th2-mediated pulmonary inflammation is poorly defined. Our data suggest a novel role for eosinophils as immune modulators that drive Th2-mediated pulmonary pathologies through activation/recruitment of Tcells and modulation of Th2 cytokines. Eosinophil infiltration into the lung and airways is a hallmark of allergic asthma, yet the role of eosinophils in immune regulation of Th2-mediated pulmonary inflammation is poorly defined. Our data suggest a novel role for eosinophils as immune modulators that drive Th2-mediated pulmonary pathologies through activation/recruitment of Tcells and modulation of Th2 cytokines. MethodsTwo independent models of acute allergic inflammation were conducted in mice congenitally devoid of eosinophils (transgenic line: PHIL) and wild type mice. Mice were either sensitized and challenged with ovalbumin (OVA) or adoptively transferred with OVA-specific (OT-II) Th2 polarized T cells and eosinophils followed by challenge with OVA. Two independent models of acute allergic inflammation were conducted in mice congenitally devoid of eosinophils (transgenic line: PHIL) and wild type mice. Mice were either sensitized and challenged with ovalbumin (OVA) or adoptively transferred with OVA-specific (OT-II) Th2 polarized T cells and eosinophils followed by challenge with OVA. ResultsPHIL mice that underwent the OVA sensitization/challenge had reduced bronchoalveolar lavage (BAL) levels of Th2 cytokines and reduced pulmonary T cell numbers as compared to wild type mice. Adoptive cell transfer studies using Th2 polarized OT-II T cells and eosinophils demonstrated that only adoptive transfer of both eosinophils and T cells increased BAL Th2 cytokines levels and accumulation of effector T cells (CD62L(-)CD44(+)) in the lungs of allergen-challenged mice. PHIL mice that underwent the OVA sensitization/challenge had reduced bronchoalveolar lavage (BAL) levels of Th2 cytokines and reduced pulmonary T cell numbers as compared to wild type mice. Adoptive cell transfer studies using Th2 polarized OT-II T cells and eosinophils demonstrated that only adoptive transfer of both eosinophils and T cells increased BAL Th2 cytokines levels and accumulation of effector T cells (CD62L(-)CD44(+)) in the lungs of allergen-challenged mice. ConclusionsEosinophil effector functions in pulmonary Th2 inflammation likely includes not only destructive effector functions, but also immune regulating roles. The data suggest eosinophils contribute to Th2 inflammation through direct and indirect modulation of Th2 cytokines. More importantly, eosinophils appear to enhance Th2 inflammation through the activation/recruitment of T cells to the lymph nodes and lungs of allergen sensitized/challenged mice, which in turn implicates an expanded role for eosinophils in the onset and maintenance of allergic asthma. Eosinophil effector functions in pulmonary Th2 inflammation likely includes not only destructive effector functions, but also immune regulating roles. The data suggest eosinophils contribute to Th2 inflammation through direct and indirect modulation of Th2 cytokines. More importantly, eosinophils appear to enhance Th2 inflammation through the activation/recruitment of T cells to the lymph nodes and lungs of allergen sensitized/challenged mice, which in turn implicates an expanded role for eosinophils in the onset and maintenance of allergic asthma.

M4 acute myeloid leukemia: the role of eosinophilia and cytogenetics in treatment response and survival. The GIMEMA experience

Myelomonocytic acute myeloid leukemia (M4-AML) is frequently associated with the cytogenetic marker inv(16) and/or the presence of eosinophilia. The aim of this study was to analyze the incidence and prognostic role of these factors in a large series of patients. Adult patients with acute myeloid leukemia consecutively enrolled in the GIMEMA trials AML10 and LAM99p were retrospectively analyzed. Among 1686 patients, 400 cases of M4-AML were identified; of these, 78% had neither eosinophilia nor inv(16), 6% had eosinophilia only, 8% had inv(16) only and 8% had both. Univariate analysis showed that both eosinophilia and inv(16) were correlated with a higher probability of complete remission, lower resistance to chemotherapy and increased overall survival. Multivariate analysis showed that the simultaneous presence of the two factors significantly increased the probabilities of both complete remission and overall survival. The presence of only one of the two factors also increased the probabilities of complete remission and overall survival, but not to a statistically significant extent. The relapse-free survival of the responding patients was not influenced by the two factors. In a large series of patients with M4-AML we confirmed the favorable role of inv(16), but the weight of this factor among the whole M4 population was of limited relevance. Eosinophilia, which affects a small proportion of cases, also emerged as a favorable prognostic factor. Based on the results of this large case population, overall and relapse-free survival rates of patients with M4-AML are not significantly better than those of patients with non-M4 AML, while the concomitant presence of both inv(16) and eosinophilia was associated with a significantly improved prognosis.

Presence of Eosinophils in Nasal Secretion during Acute Respiratory Tract Infection in Young Children Predicts Subsequent Wheezing within Two Months

In young children with wheezing or bronchiolitis, especially with respiratory syncitial virus, blood eosinophilia and a high eosinophil cationic protein level in nasal secretions predicts subsequent wheezing in later childhood. However, whether eosinophil activation results from virus-induced inflammation or local eosinophilia per se precedes the onset of wheezing remains unknown. In the present study, we examined the association between the presence of nasal eosinophils during respiratory tract infection (RTI) and subsequent wheezing in young children. A total of 35 young children less than 3 years of age who visited our outpatient clinic with rhinorrhea between April and July 2004 were enrolled in this prospective cohort study. Subjects who were given diagnoses of allergic rhinitis were excluded. In all the subjects, the presence of eosinophils in nasal secretions was determined. The subjects were followed, and the cumulative incidences of wheezing during the subsequent 2- and 12-month periods were examined. According to a logistic regression analysis adjusted for age, sex, family history, allergies, and wheezing at entry, young children with nasal eosinophil infiltration during acute RTI had a significantly higher risk of wheezing during the subsequent 2 months, compared with those without nasal eosinophil infiltration (adjusted odds ratio, 27.618, p = 0.016). Our findings not only suggest that nasal eosinophil testing may serve as a convenient clinical marker for identifying young children at risk for subsequent wheezing, but also shed new light on the role of eosinophils in the onset of wheezing in young children.

Peripheral blood eosinophilia in association with generalized pustular and erythrodermic psoriasis

In recent studies, it has been documented that the eosinophil cells play active role in many kinds of inflammatory disorders. Measurements of the mediators released by eosinophils and cell counts in serum and skin have provided some evidence indicating the role of eosinophils in psoriasis. To evaluate the blood eosinophil cell count in patients with erythrodermic psoriasis and generalized pustular psoriasis. In this study, 48 patients with histopathologically proven psoriasis (33 with erythrodermic, 15 with generalized pustular); 43 patients with maculopapular, erythematous, or bullous drug eruption with widespread involvement; and 51 patients with basal cell carcinoma were included. These three groups were compared with each other in terms of their absolute eosinophil cell counts and percentage of eosinophils. Forty-one point seven per cent of patients with psoriasis had peripheral blood eosinophilia compared with 58.1% of the patients with drug eruption and 11.8% of patients with basal cell carcinoma. The percentage of patients with eosinophilia both in patients suffering from psoriasis and drug eruption were significantly increased compared with the patients with basal cell carcinoma (P < 0.001). The absolute median eosinophil cell counts both in patients with psoriasis and drug eruption were also significantly differed from patients with basal cell carcinoma (259.2, 439.1 and 183.1, respectively; P < 0.001) Peripheral blood eosinophilia seems to be associated with severe forms of psoriasis. This finding may suggest that the eosinophils have significant roles in the pathogenesis of these types of psoriasis.

Production of monoclonal antibodies reactive with ovine eosinophils

BackgroundThere 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.ResultsA 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.ConclusionThis 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.

Different pathological phenotypes of autoimmune gastritis induced by neonatal thymectomy between BALB/c and (BALB/c × DBA/2) F1 mice: role of eosinophils in hypertrophic autoimmune gastritis

A unique pathological feature of murine autoimmune gastritis (AIG) is its pronounced mucosal hypertrophy, which is different from human type A chronic atrophic gastritis with pernicious anemia. The aim of this study was to clarify the mechanism of gastric hypertrophy in murine AIG, especially in relation to inflammatory cells infiltrating the gastric mucosa. Neonatally thymectomized (NTx) BALB/c and (BALB/c x DBA/2) F1 mice with gastritis were examined histologically and serologically. The T-helper (Th1/Th2) immune balance in the spleen was evaluated by intracellular cytokine staining for interferon-gamma and a flow-cytometric beads array for several cytokines. Additionally, NTx AIG BALB/c mice were orally administered an H(2)-blocker to decrease eosinophils. NTx AIG BALB/c mice exhibited gastritis without stomach hypertrophy at 2 months of age, and developed gastritis with mucous gland hypertrophy accompanied by eosinophil infiltration at 6 months of age. In contrast, NTx AIG (BALB/c x DBA/2) F1 mice displayed gastritis with neither stomach hypertrophy nor eosinophil infiltration even at the age of 6 months. Upregulation of interleukin-4 and granulocyte-macrophage colony-stimulating factor in the spleen was observed in BALB/c mice but not in (BALB/c x DBA/2) F1 mice. Additionally, some NTx AIG BALB/c mice did not show gastric hypertrophy or eosinophil infiltration owing to the administration of an H(2)-blocker. There are two different pathological phenotypes of murine AIG, chronic gastritis and hypertrophic gastritis, in NTx AIG BALB/c mice. Furthermore, eosinophil infiltration and the Th2 immune response might play a key role in the phenotypic shift from chronic gastritis to hypertrophic gastritis in these mice.

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.

Images in allergy and immunology: Role of eosinophils in airway remodeling

Images in allergy and immunology: Role of eosinophils in airway remodeling