Bronchial epithelial cells of patients with asthma release chemoattractant factors for T lymphocytes
Background: T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattrac...
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Published in | Journal of allergy and clinical immunology Vol. 92; no. 3; pp. 412 - 424 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
New York, NY
Mosby, Inc
01.09.1993
Elsevier |
Subjects | |
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Abstract | Background:
T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes.
Methods:
Sixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10
−6 mol/L histamine.
Results:
Only the supernatants of cells from donors with asthma showed chemotactic activity for T lymphocytes, and this was significantly increased (
p < 0.025) by exposure to histamine. Chemotactic activity was in part mediated by interkukin-8 (IL-8), because an antibody against human IL-8 significantly reduced it (
p < 0.05) and the cell supematants contained appreciable amounts of immunoreactive IL-8 (0.89 ± 0.39 ng/ml). Both the residual chemotactic activity of unstimulated epithelial cells and the increased activity caused by histamine were mediated by a single protease-sensitive substance with an apparent molecular weight of 56,000 d and an extimated isoelectric point of 8.8 to 9.1. The partially purified chemoattractant specifically enhanced the migration of CD4+ T lymphocytes, and its activity was inhibited by the univalent Fab fragment of a monoclonal antibody against CD4.
Conclusion:
These results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma. |
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AbstractList | T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes.
Sixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10(-6) mol/L histamine.
Only the supernatants of cells from donors with asthma showed chemotactic activity for T lymphocytes, and this was significantly increased (p < 0.025) by exposure to histamine. Chemotactic activity was in part mediated by interleukin-8 (IL-8), because an antibody against human IL-8 significantly reduced it (p < 0.05) and the cell supernatants contained appreciable amounts of immunoreactive IL-8 (0.89 +/- 0.39 ng/ml). Both the residual chemotactic activity of unstimulated epithelial cells and the increased activity caused by histamine were mediated by a single protease-sensitive substance with an apparent molecular weight of 56,000 d and an estimated isoelectric point of 8.8 to 9.1. The partially purified chemoattractant specifically enhanced the migration of CD4+ T lymphocytes, and its activity was inhibited by the univalent Fab fragment of a monoclonal antibody against CD4.
These results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma. Background: T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes. Methods: Sixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10 −6 mol/L histamine. Results: Only the supernatants of cells from donors with asthma showed chemotactic activity for T lymphocytes, and this was significantly increased ( p < 0.025) by exposure to histamine. Chemotactic activity was in part mediated by interkukin-8 (IL-8), because an antibody against human IL-8 significantly reduced it ( p < 0.05) and the cell supematants contained appreciable amounts of immunoreactive IL-8 (0.89 ± 0.39 ng/ml). Both the residual chemotactic activity of unstimulated epithelial cells and the increased activity caused by histamine were mediated by a single protease-sensitive substance with an apparent molecular weight of 56,000 d and an extimated isoelectric point of 8.8 to 9.1. The partially purified chemoattractant specifically enhanced the migration of CD4+ T lymphocytes, and its activity was inhibited by the univalent Fab fragment of a monoclonal antibody against CD4. Conclusion: These results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma. T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes.BACKGROUNDT lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes.Sixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10(-6) mol/L histamine.METHODSSixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10(-6) mol/L histamine.Only the supernatants of cells from donors with asthma showed chemotactic activity for T lymphocytes, and this was significantly increased (p < 0.025) by exposure to histamine. Chemotactic activity was in part mediated by interleukin-8 (IL-8), because an antibody against human IL-8 significantly reduced it (p < 0.05) and the cell supernatants contained appreciable amounts of immunoreactive IL-8 (0.89 +/- 0.39 ng/ml). Both the residual chemotactic activity of unstimulated epithelial cells and the increased activity caused by histamine were mediated by a single protease-sensitive substance with an apparent molecular weight of 56,000 d and an estimated isoelectric point of 8.8 to 9.1. The partially purified chemoattractant specifically enhanced the migration of CD4+ T lymphocytes, and its activity was inhibited by the univalent Fab fragment of a monoclonal antibody against CD4.RESULTSOnly the supernatants of cells from donors with asthma showed chemotactic activity for T lymphocytes, and this was significantly increased (p < 0.025) by exposure to histamine. Chemotactic activity was in part mediated by interleukin-8 (IL-8), because an antibody against human IL-8 significantly reduced it (p < 0.05) and the cell supernatants contained appreciable amounts of immunoreactive IL-8 (0.89 +/- 0.39 ng/ml). Both the residual chemotactic activity of unstimulated epithelial cells and the increased activity caused by histamine were mediated by a single protease-sensitive substance with an apparent molecular weight of 56,000 d and an estimated isoelectric point of 8.8 to 9.1. The partially purified chemoattractant specifically enhanced the migration of CD4+ T lymphocytes, and its activity was inhibited by the univalent Fab fragment of a monoclonal antibody against CD4.These results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma.CONCLUSIONThese results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma. T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes. Sixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10 super(-6) mol/L histamine. The results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma. |
Author | Bellini, Alberto Marini, Maurizio Yoshimura, Hiroshi Mattoli, Sabrina Vittori, Enza |
Author_xml | – sequence: 1 givenname: Alberto surname: Bellini fullname: Bellini, Alberto organization: From the Diagnostic Center for Respiratory and Allergic Diseases, Institute of Experimental Medicine, Milan, Italy – sequence: 2 givenname: Hiroshi surname: Yoshimura fullname: Yoshimura, Hiroshi organization: From the Diagnostic Center for Respiratory and Allergic Diseases, Institute of Experimental Medicine, Milan, Italy – sequence: 3 givenname: Enza surname: Vittori fullname: Vittori, Enza organization: From the Diagnostic Center for Respiratory and Allergic Diseases, Institute of Experimental Medicine, Milan, Italy – sequence: 4 givenname: Maurizio surname: Marini fullname: Marini, Maurizio organization: From the Diagnostic Center for Respiratory and Allergic Diseases, Institute of Experimental Medicine, Milan, Italy – sequence: 5 givenname: Sabrina surname: Mattoli fullname: Mattoli, Sabrina organization: From the Diagnostic Center for Respiratory and Allergic Diseases, Institute of Experimental Medicine, Milan, Italy |
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Keywords | T lymphocytes interkukin-8 PBS EC-CM FEV 1 IL EC-CF asthma PC20M Airway epithelium lymphocyte chemoattractant factor LCF Human Allergy Immunopathology Respiratory disease T-Lymphocyte Bronchus Exploration Epithelium Chemotactic factor Asthma |
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Snippet | Background:
T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways... T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still... |
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SubjectTerms | Adult Airway epithelium Allergic diseases asthma Asthma - immunology Biological and medical sciences Bronchi - immunology Bronchi - pathology Cells, Cultured Chemotactic Factors - biosynthesis Chemotaxis, Leukocyte - drug effects Chemotaxis, Leukocyte - immunology Epithelium - immunology Epithelium - pathology Female Histamine - pharmacology Humans Immunopathology interkukin-8 Interleukin-8 - biosynthesis lymphocyte chemoattractant factor Male Medical sciences Respiratory and ent allergic diseases T lymphocytes T-Lymphocytes - immunology |
Title | Bronchial epithelial cells of patients with asthma release chemoattractant factors for T lymphocytes |
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