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PubMed1996

Heterogeneity of eosinophils in chronic eosinophilic pneumonia.

It has previously been shown that patients with chronic eosinophilic pneumonia can be divided into 2 groups according to the chemotactic response of their eosinophils to 5 different eosinophil chemotactic factors (ECFs) and laboratory findings. In contrast, eosinophils obtained by bronchoalveolar lavage from both groups responded to all 5 ECFs. The correlation between the two groups and the expression of several antigens (VLA-4, CD69, ICAM-1 and CD11b) on eosinophils. The VLA-4 expression of group 1 eosinophils was higher than that of group 2 eosinophils. More interestingly, eosinophils that migrated towards ECF-PI9 expressed less CD69 than those that migrated towards other STO-2-derived ECF. The heterogeneous response of eosinophils to STO-2-derived ECFs suggests that the population of eosinophils is heterogeneous.

Antigens, CD↗
PubMed1992

[Evaluation of tissue eosinophils in eosinophilic pneumonia].

Transbronchial biopsy specimens from ten patients with eosinophilic pneumonia were analysed to see whether the tissue contained activated eosinophils or secreted eosinophil cationic protein. The specimens showed many infiltrated tissue eosinophils in the intraalveolar spaces, and thickened alveolar septae and perivascular areas. Most of these eosinophils stained clearly with degranulation by immunohistochemical studies with monoclonal antibody EG2 (for the secreted form of eosinophil cationic protein), indicating that they were activated eosinophils. On the other hand, although pleural tissue obtained at bullectomy performed after pneumothorax showed eosinophilic infiltration, EG2-positive cells were few. Activated eosinophils may play an important role in the development of pulmonary lesions of eosinophilic pneumonia.

Adolescent↗
PubMed1993

Inhibition of the activation of hageman factor (factor XII) by eosinophils and eosinophilic constituents.

Several syndromes characterized by striking eosinophilia may be complicated by thrombosis. The experiments described indicate that, paradoxically, eosinophils and certain of their constituents inhibit the activation of Hageman factor (HF, factor XII). In earlier studies, suspensions of mixed types of granulocytes, other nucleated peripheral blood cells, and platelets inhibited activation of Hageman factor by ellagic acid, glass, and sulfatides. After these cells were sedimented by centrifugation, the supernatant fluids were also inhibitory. No attempt had been made earlier to distinguish among different granulocytic species. In the present study, suspensions of eosinophils and the supernatant fluid after eosinophils had been separated by centrifugation inhibited activation of Hageman factor by ellagic acid. The protein concentration of that amount of supernatant fluid that inhibited activation by about half was 16 micrograms/ml, approximately the same as had been described for suspensions of peripheral blood mononuclear cells. Activation of Hageman factor by ellagic acid was also inhibited by certain constituents of eosinophils, including eosinophil peroxidase, eosinophil major basic protein and eosinophil cationic protein. Inhibition was not specific for ellagic acid-induced activation of Hageman factor, as inhibition was also observed with sulfatide-induced activation. Inhibition was presumably related to neutralization of the negative charge of activators of Hageman factor. Thus, bismuth subgallate, a particulate activator of Hageman factor, was no longer effective after it had been exposed to eosinophil cationic protein. The observations reported here raise the question of whether in vivo eosinophils modulate certain of the defense reactions ascribed to Hageman factor.

Blood Proteins↗
PubMed1997

Administration of G-CSF to healthy subjects: the effects on eosinophil counts and mobilization of eosinophil granule proteins.

Any influence of G-CSF on eosinophils is mostly negative, although reports which have studied this relationship are few with varied results. The aim of this study was to investigate the influence of G-CSF administration to healthy subjects on eosinophils in peripheral blood. Blood eosinophil counts, serum levels of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and eosinophil protein X (EPX), as well as cell morphology were studied. 14 healthy volunteers received 7.5 microg (n = 8) or 10 microg/kg body weight (n = 6) G-CSF daily for six consecutive days. ECP and EPX were assessed by specific RIAs and EPO by a specific FEIA. Cell morphology was examined by electron microscopy. During G-CSF administration, eosinophil counts increased from 0.22 +/- 0.04 x 10(9)/l to 0.61 +/- 0.098 x 10(9)/l (P = 0.001), serum ECP from 12.39 +/- 2.45 microg/l to 61.82 +/- 7.38 microg/l (P = 0.0014), serum EPX from 28.05 +/- 4.54 microg/l to 87.86 +/- 9.84 microg/l (P = 0.002) and serum EPO from 8.89 +/- 2.2 microg/l to 19.98 +/- 5.1 microg/l (P = 0.003). All variables returned gradually to initial values after discontinuation of G-CSF. Distinct changes in the morphology of secondary granules were observed 24 h after G-CSF administration. The granules became irregular and their matrix less electron dense. We conclude that administration of G-CSF to healthy humans increases the number of circulating eosinophils and affects the mobilization of eosinophil granule proteins.

Adult↗
PubMed1993

IgE-binding molecules (Mac-2/epsilon BP) expressed by human eosinophils. Implication in IgE-dependent eosinophil cytotoxicity.

Macrophage cell-surface protein 2 (Mac-2), a galactose specific S-type lectin identified in inflammatory macrophages, presents a high degree of homology with the rat IgE-binding protein (epsilon BP). In the present study, we show by different experimental approaches that human eosinophils can express Mac-2/epsilon BP. Flow cytometry analysis revealed that a large proportion of eosinophilic patients expressing binding sites for IgE on their eosinophil membrane, were able to bind anti-Mac-2 monoclonal antibody (mAb). Northern blot performed with eosinophil RNA hybridized with the human Mac-2 or epsilon BP cDNA probes revealed that eosinophils presented a unique transcript at 1.2 kb. Immunoprecipitation of eosinophil extracts with anti-Mac-2 mAb revealed the presence of a molecule of 29 kDa corresponding to Mac-2 protein, as well as one additional molecule of 15 kDa, absent from control alveolar macrophages. The function of these molecules was investigated in a radiolabeled IgE binding assay. Anti-Mac-2 mAb as well as galactose and lactose saccharides significantly inhibited the binding of radiolabeled human myeloma IgE protein to eosinophils. Moreover, the dose-dependent inhibition by anti-Mac-2 mAb of IgE-dependent eosinophil-mediated cytotoxicity towards parasite targets indicated the role of these IgE-binding molecules in the function of human eosinophils. These results suggest that in addition to transmembrane receptors, lectin-type molecules can participate in the IgE-dependent effector function of eosinophils.

Animals↗
PubMed2000

Inhibition of eosinophil transepithelial migration and downregulation of adhesion molecule expression on eosinophils and airway epithelial cells induced by budesonide.

In asthma, eosinophil migration through the bronchial mucosa is mediated by the expression of surface molecules on eosinophils and airway epithelial cells. To characterize the activity of budesonide on eosinophil transepithelial migration, blood eosinophils were isolated from atopic asthmatic subjects and human bronchial epithelial cells (HBECs) from surgically resected bronchi. In the presence of different concentrations of budesonide (0.1-100 nM), we tested: a) eosinophil migration induced by C5a through HBEC monolayers; b) ICAM-1 expression on HBECs, stimulated with C5a and c) LFA-1 and Mac-1 expression on eosinophils, stimulated with C5a or with ah-CD23 mabs plus GM-CSF. Eosinophils showed a remarkable chemotactic response to C5a (P<0.001), that was effectively down-regulated by the presence in the chemotactic chambers of budesonide at all the concentrations tested (P<0.05). A weaker, but still present, inhibitory activity on cell locomotion was observed when HBECs or eosinophils were preincubated with budesonide before the chemotaxis assay, which was performed in absence of the drug. Preincubation of the cells with different concentrations of budesonide was also effective in down-regulating the C5a-induced ICAM-1 expression on HBECs and the ah-CD23 and GM-CSF-induced LFA-1 and Mac-1 expression on eosinophils. Thus, budesonide-induced down-regulation of eosinophil migration through airway epithelial cells is associated with, and possibly partially dependent on inhibition of adhesion molecule expression on both cell types.

Adolescent↗
PubMed2001

Nitric oxide regulates human eosinophil adhesion mechanisms in vitro by changing integrin expression and activity on the eosinophil cell surface.

1. The nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), inhibits both rat and human eosinophil chemotaxis in vitro. Here, the role of nitric oxide (NO) in human eosinophil cell surface integrin expression and function was investigated. 2. Human peripheral blood eosinophils were treated with L-NAME (0.01 - 1.0 mM) and their adhesion to human fibronectin and serum observed. Adhesion of cells to fibronectin and serum increased by 24.0+/-4.6 and 43.8+/-4.7%, respectively, when eosinophils were treated with 1.0 mM L-NAME. Increased adhesion by L-NAME could be abolished when cells were co-incubated with VLA-4- and Mac-1-specific monoclonal antibodies (mAbs). 3. The NO donor, sodium nitroprusside (2.5 mM), significantly inhibited eosinophil adhesion to fibronectin and serum by 34.3+/-4.5 and 45.2+/-5.6%, respectively. This inhibition was accompanied by a 4 fold increase in the levels of intracellular cyclic GMP. 4. Flow cytometrical analysis demonstrated that L-NAME induced an increased expression of CD11b (Mac-1) on the eosinophil cell surface of 36.3+/-7.4%. L-NAME had no effect upon CD49d (VLA-4) expression. 5. Treatment of human eosinophils, in vitro, with H-[1,2,4] oxadiazolo quinoxalin-1-one (ODQ) (0.1 mM), an inhibitor of soluble guanylate cyclase, also significantly increased eosinophil adhesion to fibronectin and serum by 73.5+/-17.9 and 91.7+/-12.9%, respectively. This increase in adhesion could also be inhibited by co-incubation with the Mac-1 and VLA-4-specific mAbs. 6. In conclusion, results indicate that NO, via a cyclic GMP-dependent mechanism, inhibits the adhesion of human eosinophils to the extracellular matrix (ECM). This inhibition is accompanied by a decrease in the expression and function of the eosinophil's adhesion molecules, in particular, the expression of the Mac-1 integrin and the function of the VLA-4 integrin.

Cell Adhesion↗
PubMed2003

Analysis of gene expression in peripheral blood eosinophils from patients with atopic dermatitis and in vitro cytokine-stimulated blood eosinophils.

Investigation of differentially expressed genes in eosinophils of patients with allergic diseases such as atopic dermatitis (AD) will provide important information for elucidating possible mechanisms of pathology. To identify novel genes that are expressed in AD, we compared gene expression in samples of peripheral blood eosinophils from AD patients and healthy volunteers. RNA was extracted from peripheral blood eosinophils. The expression of various genes, such as those for cytokine receptors, eosinophil activation marker, platelet activating factor (PAF) receptor, eosinophil-specific granular proteins and apoptosis-related genes, was confirmed using real-time reverse transcription-polymerase chain reaction (RT-PCR). Peripheral blood eosinophils of healthy volunteers were also isolated and stimulated for introduction of various cytokines. RNA was extracted and gene expression was monitored. Several genes, such as those for cytokine receptors (granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha and beta chain and interleukin (IL)-3 receptor alpha chain), CD44 and PAF receptor were expressed at significantly higher levels in AD patients than in healthy volunteers. In addition, the anti-apoptotic genes, bcl-2 and bcl-xL, were expressed at increased levels in AD patients. No single gene expression correlated with clinical markers, such as eosinophil count or IgE levels. Expression of GM-CSF receptor beta chain and IL-3 receptor alpha chain in isolated blood eosinophils of healthy volunteers was stimulated by IL-5, IL-4, interferon (IFN)-gamma and GM-CSF. Expression of bcl-2 and bcl-xL was also increased after stimulation with IL-5, IL-4 or IFN-gamma. The in vitro enhancement of cytokine-stimulated gene expression correlated well with the enhancement observed in clinical samples of eosinophils, suggesting that cytokines may affect gene expression in vivo in eosinophils of patients with AD.

Adolescent↗
PubMed1998

Eosinophil-mediated killing of Haemonchus contortus larvae: effect of eosinophil activation and role of antibody, complement and interleukin-5.

Eosinophils have previously been shown to accumulate around the tissue invasive (L3) stage of sheep gastrointestinal parasites in vivo. In this study, eosinophils obtained from mammary washes of sheep, were shown to immobilize and kill H. contortus larvae in vitro in the presence of antibody specific against a defined L3 surface antigen. Eosinophils obtained from sheep primed by repeated infusion of H. contortus larvae were more effective than eosinophils obtained after a single infusion of parasite extract in Fasciola hepatica infected ewes suggesting the former were activated in vivo. The level of larval immobilization in the presence of antibody was significantly increased when complement was added to cultures containing activated eosinophils. The addition of interleukin-5 to larval cultures containing antibody and complement resulted in a significant increase in larval immobilization with unactivated eosinophils suggesting that eosinophil effector function is enhanced following priming with this cytokine. Ultrastructural analysis of the eosinophil/larvae interaction at 6 h of incubation revealed degranulation of adhering eosinophils onto the surface of larvae. By 24 h of incubation, many larvae showed signs of damage and most eosinophils had degenerated. These results suggest that eosinophil-mediated killing may be an effector mechanism for the elimination of L3 H. contortus larvae in immune sheep.

Animals↗
PubMed2001

A report from the International Eosinophil Society: eosinophils in a tug of war.

The International Eosinophil Symposium in Banff was a timely gathering of leading experts to discuss the precise role of eosinophils in allergic asthma. The meeting followed hard on the heels of a report suggesting that eosinophils might be redundant in late-phase responses in asthma, inasmuch as treatment of asthmatic patients with humanized anti-IL-5 in clinical trials failed to modify bronchial hyperresponsiveness. Mouse models of allergic asthma were also cited for failing to show a consistent proinflammatory role for the eosinophil in asthma. Presentations at this meeting included a reevaluation of murine models of asthma, which exhibit substantial differences from human disease. The inability of murine eosinophils to degranulate either in vivo or in vitro was shown to present a major obstacle in asthma research; this is in sharp contrast to human eosinophils, which readily degranulate in response to stimuli. Degranulation from eosinophils was proposed to be a crucial event in human airway hyperresponsiveness. Major advances were presented in the understanding of molecular and intracellular pathways regulating eosinophil priming, activation, and mediator secretion. Recruitment and activation of eosinophils might be regulated by other immunoregulatory agents as well as IL-5, including eotaxin. Future clinical trials might benefit from focusing on dual inhibition of IL-5 and eotaxin to ensure the removal of the effects of activated eosinophils from the body.

Animals↗
PubMed2003

Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics.

BACKGROUND: Eosinophils develop from CD34(+) progenitors under the influence of IL-5. Atopic asthmatic individuals have increased numbers of mature eosinophils and eosinophil pro-genitors within their bone marrow and bronchial mucosa. We have previously reported that anti-IL-5 monoclonal antibody treatment decreases total bone marrow and bronchial mucosal eosinophil numbers in asthma. OBJECTIVE: Using an anti-IL-5 monoclonal antibody, we examined the role of IL-5 in eosinophil development within the bone marrow and bronchial mucosa in asthma. METHODS: Blood, bone marrow, and airway mucosal biopsy specimens were examined before and after anti-IL-5 (mepolizumab) treatment of asthmatic individuals in a double-blind, placebo-controlled trial. Numbers of mature and immature eosinophils were measured by histologic stain (bone marrow myelocytes, metamyelocytes, and mature eosinophils), flow cytometry (bone marrow and blood CD34(+)/IL-5Ralpha(+) cells), enumeration of bone marrow-derived eosinophil/basophil colony-forming units in methylcellulose culture, and sequential immunohistochemistry and in situ hybridization (bronchial mucosal CD34(+)/IL-5Ralpha mRNA(+) cells). RESULTS: Mepolizumab decreased mature eosinophil numbers in the bone marrow by 70% (P =.017) in comparison with placebo and decreased numbers of eosinophil myelocytes and metamyelocytes by 37% (P =.006) and 44% (P =.003), respectively. However, mepolizumab had no effect on numbers of blood or bone marrow CD34(+), CD34(+)/IL-5Ralpha(+) cells, or eosinophil/basophil colony-forming units. There was a significant decrease in bronchial mucosal CD34(+)/IL-5Ralpha mRNA(+) cell numbers in the anti-IL-5 treated group (P =.04). CONCLUSION: These data suggest that anti-IL-5 therapy might induce partial maturational arrest of the eosinophil lineage in the bone marrow. The reduction in airway CD34(+)/IL-5 mRNA(+) cell numbers suggests that IL-5 might also be required for local tissue eosinophilopoiesis.

Antibodies, Monoclonal↗
PubMed1977

Antibody-dependent eosinophil-mediated damage to 51Cr-labeled schistosomula of Schistosoma mansoni: damage by purieid eosinophils.

After earlier observations that antibody-dependent, cell-mediated damage to 51Cr-labeled schistosomula can be ablated by pretreatment of a mixed preparation of human peripheral blood leukocytes with an anti-eosinophil serum and complement, we investigated the cytotoxic effects of eosinophil-enriched cell preparations. Preparations containing up to 98.5% eosinophils and devoid of neutrophils were effective in mediating antibody-dependent damage to schistosomula. Preparations enriched in mononuclear cells or in neutrophils, and devoid of eosinophils, were inactive. Eosinophils from some patients with eosinophilia induced by schistosomiasis were less active on a cell-to-cell basis than cells from normal individuals. The possibility that such cells were initially blocked by immune complexes was considered, and it was found that reasonable cytotoxicity by purified eosinophils from patients with eosinophilia could be generated by overnight cultures. A possible requirement for cooperation between eosinophils and other cell types was also studied. Lymphocytes, neutrophils and monocytes failed to enhance eosinophil-mediated cytotoxicity. These results provide further evidence that the eosinophil is the only cell in man responsible for antibody-dependent, complement-independent damage to schistosomula in vitro. Eosinophils from individuals, however, differ in their cytotoxic potential by a mechanism yet to be elucidated. The possible relationship of these findings to immunity in vivo is discussed.

Animals↗
PubMed1979

Interactions between human eosinophils and schistosomula of Schistosoma mansoni. II. The mechanism of irreversible eosinophil adherence.

Previous work (1)(1) has shown that normal human eosinophils show a preferential capacity, in comparison with neutrophils, to bind to antibody- coated schistosomula of Schistosoma mansoni. This effect is attributable to a temperature-dependent function of the eosinophil which renders its binding stable and irreversible by aggregated gamma globulin or Staphylococcus aureus protein A. In contrast, the binding of neutrophils is readily reversible by these agents. It has now been shown that the differences observed between eosinophils and neutrophils is a property of their interaction with living schistosomula. When dead or artificially damaged schistosomula were tested, neutrophils showed a markedly enhanced capacity to adhere, in both the presence and absence of anti-chistosomular serum. Subsequent experiments were designed to test the hypothesis that the strong, stable binding of eosinophils was attributable to degranulation, with release of granule contents which would then serve as ligands to bind the cell to the organism. First, an enhanced adherence both of eosinophils and of neutrophils could be demonstrated in the presence of eosinophil major basic protein (MBP) or of protamine, a high molecular weight cation. Second, the binding of eosinophils induced by concanavalin A (Con A) was found to differ markedly from that induced by antischistosomular serum. Con A-mediated binding of eosinophils was fully reversible by alpha-methyl-mannoside, was not associated with damage to the organism, and did not lead to degranulation of the cell, as estimated by measuring the release of MBP into the culture supernate. However, induction of degranulation of concanavalin A-bound eosinophils, but not of neutrophils, with the calcium ionophore A23187 converted the reaction into one which was no longer reversible by alpha- methylmannoside and in which damage to the organism now did occur. These findings support the hypothesis that the stable binding of eosinophils is associated with degranulation, a process which may contribute to the preferential capacity of this cell to mediate antibody-dependent damage to schistosomula.

Antibodies↗
PubMed1985

Identification of a lymphokine that stimulates eosinophil differentiation in vitro. Its relationship to interleukin 3, and functional properties of eosinophils produced in cultures.

Factors stimulating eosinophil differentiation in vitro have been studied by means of a liquid bone marrow culture system in which the number of eosinophils is estimated directly by morphology or indirectly by assay for eosinophil peroxidase. The results show that eosinophil colonies are not formed in agar, emphasizing the importance of the liquid culture system. Three types of evidence identify a novel lymphokine, eosinophil-differentiating factor (EDF). (a) Coordinate analysis of lymphokine activity in media conditioned by a panel of parasite antigen and another panel of alloantigen-reactive T cell clones indicates that EDF is distinct from interleukin 2 (IL-2), IL-3, and bone marrow proliferation activity (BMPA). (b) A T hybrid (NIMP-TH1) produces EDF but no IL-2, IL-3, interferon, or colony-stimulating factor. (c) Gel filtration of conditioned media (CM) indicates that NIMP-TH1 and a T clone (NIMP-T2) produce EDF (Mr 46,000). NIMP-T2 also produced IL-3 (Mr 26,000) but this was easily separated from EDF. IL-3 is also shown to have eosinophil differentiation activity (EDA) but this represents a very small proportion of the EDA in T2-CM. Fractionation of WEHI-3-CM indicates that EDA from this source has a similar elution profile to IL-3 (Mr 35-36,000). Furthermore, a comparison of the relative activities in purified IL-3 and WEHI-3-CM indicates that all the EDA can be attributed to the IL-3 in the latter. EDF is shown to stimulate production of eosinophils in long-term bone marrow cultures; the kinetics of eosinophil production suggests that EDF is acting on committed precursors in the bone marrow. The transient nature of eosinophil production suggests that precursors from multipotential stem cells are not produced. The eosinophils produced in these cultures are morphologically normal and functional in that they lysed sheep red blood cells coated with IgG1, IgG2a, and IgG2b, but not with IgM, IgA, or IgE. In addition, they were capable of adhering to and killing Schistosoma mansoni schistosomula.

Animals↗
PubMed2005

Eosinophil chemoattractants in the middle ear of patients with eosinophilic otitis media.

BACKGROUND: Patients with intractable otitis media associated with bronchial asthma have an extensive accumulation of eosinophils in the effusion and mucosa of the middle ear; this condition is called eosinophilic otitis media (EOM). It remained to be determined how eosinophils accumulate in the middle ear. OBJECTIVES: To clarify the pathogenesis of middle ear diseases, we measured the concentration of eosinophil chemoattractants in middle ear effusion (MEE), and carried out immunohistochemical studies of middle ear mucosa specimens to demonstrate the expression of eosinophil chemoattractants. METHODS: Middle ear effusion samples were obtained from 15 EOM patients with bronchial asthma and from six controls for the measurement of eosinophil cationic protein (ECP), IL-5, eotaxin and regulated on activation, normal T expressed and secreted concentrations. Middle ear mucosa samples were also taken from 14 EOM patients and 16 controls for immunohistochemical study. In 10 EOM patients, the numbers of immunoreactive cells as well as apoptotic cells were determined before and after the topical application of triamcinolone acetonide into the middle ear. RESULTS: In EOM, significantly higher ECP and IL-5 concentrations were detected in MEE than in serum, and ECP, IL-5 and eotaxin concentrations in MEE were higher in the EOM patients than in the controls. ECP concentration positively correlated with that of IL-5. Immunohistochemically, the numbers of cells positive for EG2 and ecalectin were significantly higher in the EOM patients than in the controls. After the topical application of triamcinolone acetonide, the numbers of infiltrating cells and immunoreactive cells distinctly decreased, whereas the number of apoptotic cells significantly increased. CONCLUSION: In EOM, locally produced IL-5 may play a crucial role in the accumulation of eosinophils in the middle ear. Chemokines such as ecalectin and eotaxin are also produced in the middle ear, and help activate and enhance the survival of eosinophils to induce the intractable condition in the middle ear. The topical application of triamcinolone acetonide induces the apoptosis of not only eosinophils but also eosinophil chemoattractant-producing cells, thereby improving the middle ear condition.

Adult↗
PubMed1984

Eosinophil cationic protein in inflammatory synovial effusions as evidence of eosinophil involvement.

Eosinophils are seldom noted in inflammatory synovial fluids but are reported to infiltrate the synovial tissue in inflammatory arthritides. To elucidate a possible role for eosinophils in inflammatory joint reactions the concentrations of eosinophil cationic protein (ECP)--a specific granule protein from eosinophils--were measured by radioimmunoassay in 90 synovial fluids from patients with various inflammatory arthritides (rheumatoid arthritis, reactive and crystal arthritides, Reiter's disease and psoriatic arthropathy). In the same specimens lactoferrin was measured as an indicator of neutrophil-involved inflammation. In comparison with the normal circulating levels of ECP and lactoferrin the measured synovial fluid concentrations of both proteins were considerably raised in all patient groups with inflammatory joint diseases in contrast to patients with non-inflammatory arthritides. There was a striking positive correlation between the ECP and lactoferrin synovial fluid concentrations. These data indicate that eosinophil activation is prominent in inflammatory joint reactions and is linked to the activation of neutrophils. The regulation of degranulation or secretion by eosinophils is unknown. Our in-vitro studies showed that peripheral blood isolated neutrophils as well as eosinophils degranulated when exposed to IgG complexes. However, eosinophil degranulation was modest compared with neutrophil degranulation. These data suggest that neutrophil phagocytosis of, for example, immune complexes may be one major mechanism in neutrophil degranulation but that other factors determine the appearance of eosinophil products in inflammatory synovial effusions. The possible modulatory or harmful role of eosinophils in inflammatory joint disease can at present only be speculated on.

Adolescent↗
PubMed2001

Interleukin-5 induces CD34(+) eosinophil progenitor mobilization and eosinophil CCR3 expression in asthma.

Asthma is characterized by the accumulation of activated T cells and eosinophils within the airway. Eosinophils derive from CD34(+) bone marrow progenitor cells under the influence of hematopoietic growth factors, subsequently migrating to the airways under the cooperative influence of interleukin (IL)-5 and chemokines, including eotaxin. We compared the relative effects of systemic versus local IL-5 on progenitor-cell mobilization and mature eosinophil phenotype by using flow cytometry, following the administration of intravenous (2 microg) or inhaled (15 microg) IL-5 to nine patients with mild asthma. Intravenous IL-5 induced a rapid reduction in circulating eosinophil counts followed by prolonged blood eosinophilia. Both intravenous (p < 0.002) and inhaled (p < 0.05) IL-5 significantly increased CD34(+)/CD45(+) lymphoblastoid eosinophil progenitors. Intravenous IL-5 increased mature eosinophil CCR3 expression from a baseline mean fluorescence intensity (MFI) of 658 +/- 51.7 to 995 +/- 93.2 at 24 h (p < 0.05), but had no effect on interleukin-5 receptor subunit alpha or CD11b expression. Lymphocyte CCR3 MFI was increased by intravenous IL-5 from 38.5 +/- 13.6 at baseline to 73.6 +/- 14.3 at 24 h (p < 0.05). Systemic IL-5 increased circulating eosinophil progenitors, suggesting a key role for systemic IL-5 in eosinophil mobilization. Further, IL-5 causes terminal maturation of the eosinophil by increasing CCR3 expression, potentially affecting CCR3-dependent chemotaxis by eosinophils and lymphocytes.

Adult↗
PubMed2004

Deletion of the major GATA1 enhancer HS 1 does not affect eosinophil GATA1 expression and eosinophil differentiation.

Expression of the myeloid transcription factor GATA1 is required for early stages of eosinophil differentiation. Defining mechanisms regulating eosinophil GATA1 expression will be important to understand development of this lineage. However, the cis-elements required for eosinophil GATA1 expression are not fully characterized. Previous work identified HS 1 as a major GATA1 enhancer, but its role in eosinophil GATA1 expression is unclear. Here, we show that mouse HS 1 deletion leaves eosinophil GATA1 mRNA expression and eosinophil differentiation unaffected. Chromatin isolated from eosinophils and encompassing HS 1 is weakly enriched for acetylated histones H3/H4. HS 1 deletion does not alter eosinophil GATA1 locus histone acetylation. In eosinophils, GATA1 and CCAAT/enhancer binding protein epsilon (C/EBP epsilon) do not bind HS 1 but bind selectively a cis-element in the first GATA1 intron. Thus, HS 1 is not required for eosinophil GATA1 expression. Instead, this study suggests a previously unsuspected role for the GATA1 intron element for this function.

Acetylation↗