Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma (original) (raw)
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Macrophage migration inhibitory factor (MIF) in bronchial asthma
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2000
Background Macrophage migration inhibitory factor (MIF) is a pro-in¯ammatory cytokine favouring the secretion of TNFa and IL-8 and counteracts anti-in¯ammatory effects of corticosteroids. Airways in¯ammation is a central feature of bronchial asthma and is characterized by the accumulation of eosinophils. Objective The aim of this study was to investigate whether MIF is related to asthma symptoms and eosinophil accumulation in the airways. Methods Serum MIF levels were measured by an enzyme-linked immunosorbent assay in 44 healthy subjects and 44 asthmatics. Levels of MIF in induced sputum were measured in 10 healthy subjects and 15 asthmatics. Levels of eosinophil cationic protein (ECP) in induced sputum were measured by a radioimmunosorbent assay. Fluorescence double immunostaining was conducted to examine cellular source and localization of MIF. Results Serum MIF levels were signi®cantly increased in asthmatic patients compared with age and sex-matched control subjects. Symptomatic patients had a higher MIF level than asymptomatic patients. Induced sputum obtained from asthmatics contained higher levels of MIF than those from control subjects. MIF levels in induced sputum were correlated with ECP levels in induced sputum. MIF was colocalized with eosinophil peroxidase staining in the cytoplasm of sputum cells. Conclusion Increased MIF levels are associated with asthma symptoms and one of the cellular sources of MIF in the airways are eosinophils.
The European respiratory journal, 1994
Increasing evidence implicates the eosinophil as an important effector cell in asthma, but little is known regarding its regulation in vivo. Granulocytemacrophage colony-stimulating factor (GM-CSF) has been shown to regulate eosinophil function in vitro. We investigated the in vivo role of eosinophils and GM-CSF in mild asthma. We compared the number and function of eosinophils and the presence of GM-CSF in blood, bronchoalveolar lavage (BAL) and biopsy tissue obtained from eight mild, stable, atopic asthmatics and 10 nonasthmatics, five of whom were atopic and five nonatopic. Eosinophils were significantly increased in the blood, BAL and biopsy tissue from asthmatics. Activated eosinophils, assessed by immunostaining for the secreted form of eosinophil cationic protein (EG2), were also increased in asthmatic BAL cells and biopsy tissue. Significant increases in GM-CSF in BAL cells and biopsy tissue from asthmatics were also evident. Significant positive correlations existed between GM-CSF in BAL and EG2, and GM-CSF in biopsy tissue and BAL and biopsy eosinophils. Airway responsiveness was also significantly positively correlated with eosinophil number and activation, and with GM-CSF. These results demonstrate that there are increased numbers of activated eosinophils and GM-CSF is increased in patients with mild asthma. Furthermore, GM-CSF is correlated with eosinophil number and function in vivo and these indices are significantly correlated with airway function. These findings emphasize the importance of eosinophils, potentially regulated in vivo by GM-CSF, in contributing to the disordered airway function evident even in mild asthma.
Journal of Allergy and Clinical Immunology, 1995
Eosinophils are hypothesized to be crucial in the development of allergic airway inflammation; however, the actual mechanisms that determine their inflammatory activity are still largely undefined. To investigate the factors that regulate eosinophil function in allergic airway disease, we have previously used segmental bronchoprovocation with allergen to study ex vivo eosinophil function. To determine whether the functional changes associated with airway eosinophils obtained by bronchoalveolar lavage 48 hours after antigen challenge are caused by exposure to airway-generated cytokines, normodense blood eosinophils were cultured in vitro with recombinant human interleukin-5 (IL-5) or granulocyte-macrophage colony stimulating factor (GM-CSF). The effect of cytokine exposure was then evaluated on selected cell functions. In vitro incubation with these cytokines for 24 hours significantly increased eosinophil membrane expression of CD18 and CD I lb compared with culture in medium alone or eosinophils obtained by bronchoalveolar lavage. N-formyl-methionyl-leucylphenylalanine-stimulated superoxide anion generation was slightly but significantly enhanced by incubation with IL-5 but not with GM-CSF. In addition, spontaneous adhesion to human umbilical vein endothelial cell monolayers was increased after exposure to both IL-5 and GM-CSF. However, activated adhesion was enhanced only by culture with IL-5 and stimulation with N-formyl-methionyl-leucyl-phenylalanine. The magnitude of functional changes after in vitro preincubation of eosinophils with these cytokines did not achieve levels of superoxide anion and adhesion noted with airway eosinophils obtained after segmental bronchoprovocation with allergen. These observations raise the possibility that the contribution of IL-5 and GM-CSF to phenotypic changes of airway eosinophils is principally to enhance survival and expression of adhesion proteins. These data also suggest that, in addition to the generation of proinflammatory cytokines, other factors contribute to phenotypic changes in eosinophils as they migrate from the blood to the airway.
Journal of Allergy and Clinical Immunology, 2010
Background: Noneosinophilic asthma is common across asthma severities. However, in patients with moderate-to-severe disease, the absence of sputum eosinophilia cannot distinguish between asthmatic subjects with eosinophilic inflammation controlled by corticosteroids versus those in whom eosinophilic inflammation is not a component of the disease. Objectives: We sought to develop a method to quantify eosinophil proteins in airway macrophages as a novel biomarker of eosinophilic airway inflammation. Methods: Eosinophil proteins in airway macrophages were assessed by means of flow cytometry, immunofluorescence, and cytoplasmic hue change after ingestion of apoptotic eosinophils. Airway macrophage median percentage of red-hued area in stained sputum cytospin preparations was assessed by means of image analysis from (1) subjects with mild-to-severe asthma, subjects with nonasthmatic eosinophilic bronchitis, and healthy control subjects; (2) subjects with eosinophilic severe asthma after treatment with prednisolone; and (3) subject with noneosinophilic asthma before corticosteroid withdrawal. Results: Eosinophil proteins were detected in airway macrophages, and cytoplasmic red hue increased after ingestion of apoptotic eosinophils. Airway macrophage percentage redhued area was increased in subjects with moderate-to-severe asthma compared with that seen in subjects with mild asthma and healthy control subjects, was similar in those with or without a sputum eosinophilia, and was increased after corticosteroid therapy. In asthmatic subjects without sputum eosinophilia, the airway macrophage percentage red-hued area was increased in subjects who did versus those who did not have sputum eosinophilia after corticosteroid withdrawal. Conclusions: Eosinophil proteins can be reliably measured in airway macrophages. In combination with sputum eosinophilia, the macrophage eosinophil protein content might further define the asthma phenotype and provide an additional tool to direct therapy. (J Allergy Clin Immunol 2010;126:61-9.) for help in sample collections, processing, and image acquisition.
American Journal of Respiratory and Critical Care Medicine, 1995
Allergen inhalation challenge is associated with increases in eosinophil number and activation, and provides a useful model for investigating airway inflammation in asthma. Limited information, however, is available on the effect of allergen challenge on cytokines regulating eosinophil function. We investigated allergeninduced changes in eosinophil number and activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine known to regulate eosinophil function in vitro. Seven subjects with mild atopic asthma and late asthmatic responses completed diluent-and allergen-inhalation challenges. Blood, bronchoalveolar lavage fluid (BALF), and biopsy samples were collected 24 h after challenge. Allergen inhalation caused a significant increase in eosinophils in BALF and biopsy samples. Eosinophil activation, as assessed by secretion of eosinophil cationic protein, and GM-CSF levels were significantly increased in BALF and bronchoalveolar lavage (BAL) cells. Allergen inhalation did not cause a significant change in eosinophil activation in biopsy tissue but did result in a significant decrease in GM-CSF in the tissue. Significant correlations were shown between the concentration of GM-CSF in BALF and the percentage of BAL eosinophils (Rs = 0.75, P = 0.05), severity of the late asthmatic response, and number of BAL eosinophils (Rs = 0.82, P = 0.02). A trend was seen between the late response and the concentration of GM-CSF in BALE These results are consistent with the hypothesis that eosinophils, regulated by GM-CSF, contribute to allergen-induced decreases in airway function. Woolley KL, Adelroth E, Woolley MJ, Ellis R, Jordana M, O'Byrne PM. Effects of allergen challenge on eosinophils, eosinophil cationic protein, and granulocyte-macrophage colony-stimulating factor in mild asthma.
Eosinophils and eosinophil products in asthma
Journal of Ayub Medical College, Abbottabad : JAMC, 2002
Eosinophils are known to be an indirect marker of airway inflammation in asthma. It is known since long that the total eosinophil count reflects asthmatic activity and is useful for regulating steroid dosage and for early detection of exacerbations. Eosinophils are currently regarded as the effector cells responsible for much of the pathology of asthma. Eosinophil-mediated damage to the respiratory epithelium is a major pathogenetic mechanism in asthma. This article is a review of the latest works about the relationship of eosinophil and eosinophil products with asthma.
Journal of Inflammation
We aimed to investigate peripheral blood eosinophil chemotaxis, generation of spontaneous reactive oxygen species (ROS), and apoptosis in patients with allergic asthma after bronchial allergen challenge. A total of 18 patients with allergic asthma (AA), 14 with allergic rhinitis (AR), and 10 healthy subjects (HS) underwent bronchial challenge with a specific allergen extract. Eosinophils from peripheral blood were isolated 24 h before as well as 7 and 24 h after bronchial allergen challenge. Chemotaxis, spontaneous ROS production in eosinophils, and apoptosis were analyzed by flow cytometry. Serum and induced sputum IL-5 levels were measured by ELISA; the cell count in sputum was analyzed by the May-Grünwald-Giemsa method. Before bronchial allergen challenge, peripheral blood eosinophil chemotaxis, spontaneous ROS production was enhanced and eosinophil apoptosis was reduced in the patients with AA as compared with AR patients and HS (P < 0.05). Meanwhile, eosinophil chemotaxis an...