Apoptosis, proliferation, and expression of Bcl-2, Fas, and Fas ligand in bronchial biopsies from asthmatics.

The in situ apoptosis and the expression of molecules involved in this process, such as Bcl-2, Fas, and its ligand, Fas ligand (FasL), were examined in bronchial biopsies from healthy control subjects and from steroid-untreated or -treated asthmatics, using terminal transferase-mediated deoxyuridyltriphosphate nick-end labeling and immunohistochemical techniques, respectively. Bronchial submucosa from steroid- untreated asthmatics showed an increase in the number of eosinophils and a decrease in that of apoptotic cells compared with that of control subjects, but no significant changes in the number of T lymphocytes or in that of cells expressing Bcl-2, Fas, or FasL. Treatment with steroids reduced airway eosinophilia and augmented the proportion of apoptotic eosinophils. Compared with control subjects or untreated patients, steroid-treated asthmatics exhibited increased expression of Bcl-2, Fas, FasL, and of proliferating cell nuclear antigen (PCNA) in their bronchial epithelium, without changes in the number of apoptotic cells. Moreover, the intensity of the expression of Bcl-2, Fas, and FasL correlates well with that of PCNA. We conclude that steroids may reduce the inflammatory cell infiltrate in the bronchial submucosa in part by promoting eosinophil apoptosis and by inducing the expression of FasL on bronchial epithelial cells. Treatment with steroids may also augment survival and proliferation of epithelial cells, possibly via the expression of Bcl-2 and PCNA.

[1]  M. Arock,et al.  Human eosinophils express bcl-2 family proteins: modulation of Mcl-1 expression by IFN-gamma. , 1998, American journal of respiratory cell and molecular biology.

[2]  K. Elsegood,et al.  Pasl expression on epithelial cells: the Bottazzo-Feldmann hypothesis revisited , 1997 .

[3]  P. Sterk,et al.  Enhanced expression of neutral endopeptidase (NEP) in airway epithelium in biopsies from steroid- versus nonsteroid-treated patients with atopic asthma. , 1997, American journal of respiratory cell and molecular biology.

[4]  S. Schreiber,et al.  Fas signal transduction triggers either proliferation or apoptosis in human fibroblasts. , 1997, The Journal of investigative dermatology.

[5]  K. Kuwano,et al.  Apoptosis and expression of Fas/Fas ligand mRNA in bleomycin-induced pulmonary fibrosis in mice. , 1997, American journal of respiratory cell and molecular biology.

[6]  S. Rennard,et al.  Repair mechanisms in asthma. , 1996, The Journal of allergy and clinical immunology.

[7]  E. Johnson,et al.  Nerve Growth Factor Induces the Expression of Certain Cytokine Genes and bcl-2 in Mast Cells , 1996, The Journal of Biological Chemistry.

[8]  Konrad M. Hartung,et al.  Expression and function of the Fas receptor on human blood and tissue eosinophils , 1996, European journal of immunology.

[9]  P. Kiener,et al.  Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes: implications for the regulation of apoptosis in neutrophils , 1996, The Journal of experimental medicine.

[10]  A. J. Wilson,et al.  Eosinophil apoptosis and the resolution of airway inflammation in asthma. , 1996, American journal of respiratory and critical care medicine.

[11]  E. Solary,et al.  The role of apoptosis in the pathogenesis and treatment of diseases. , 1996, The European respiratory journal.

[12]  J. M. Cousin,et al.  Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. , 1996, Journal of immunology.

[13]  L. French,et al.  Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover , 1996, The Journal of cell biology.

[14]  J. Tschopp,et al.  Activated B cells express functional Fas ligand , 1996, European journal of immunology.

[15]  S. Chouaib,et al.  Fas-mediated apoptosis in cultured human eosinophils. , 1996, Blood.

[16]  S. Durham,et al.  Prednisolone treatment in asthma. Reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa. , 1996, American journal of respiratory and critical care medicine.

[17]  E. Lalani,et al.  bcl-2: role in epithelial differentiation and oncogenesis. , 1996, Human pathology.

[18]  M. Jordana,et al.  Interleukin-3 in bronchial biopsies from nonasthmatics and patients with mild and allergen-induced asthma. , 1996, American journal of respiratory and critical care medicine.

[19]  P. Musiani,et al.  Spontaneous and glucocorticoid-induced apoptosis in human mature T lymphocytes. , 1995, Blood.

[20]  E. Lacy,et al.  Th1 CD4+ lymphocytes delete activated macrophages through the Fas/APO-1 antigen pathway. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[21]  John Calvin Reed,et al.  Immunoblot analysis of cellular expression of Bcl-2 family proteins, Bcl-2, Bax, Bcl-X and Mcl-1, in human peripheral blood and lymphoid tissues. , 1995, International immunology.

[22]  J. Erikson,et al.  Fas receptor expression on B‐lineage cells , 1995, European journal of immunology.

[23]  K. Matsumoto,et al.  Induction of apoptosis in human eosinophils by anti-Fas antibody treatment in vitro. , 1995, Blood.

[24]  E. Wang,et al.  Senescent human fibroblasts resist programmed cell death, and failure to suppress bcl2 is involved. , 1995, Cancer research.

[25]  I. Vermes,et al.  Apoptosis and inflammation , 1995, Mediators of inflammation.

[26]  M. Jordana,et al.  Granulocyte-macrophage colony-stimulating factor, eosinophils and eosinophil cationic protein in subjects with and without mild, stable, atopic asthma. , 1994, The European respiratory journal.

[27]  I. N. Crisps,et al.  Fatal interactions: fas-induced apoptosis of mature T cells , 1994 .

[28]  W. Luttmann,et al.  Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part II). , 1994, The European respiratory journal.

[29]  John Calvin Reed.  Bcl-2 and the regulation of programmed cell death , 1994, The Journal of cell biology.

[30]  D. Cosman.  A family of ligands for the TNF receptor superfamily , 1994, Stem cells.

[31]  S. Holgate,et al.  The 1992 Cournand Lecture. Asthma: past, present and future. , 1993, The European respiratory journal.

[32]  W. Sewell,et al.  Inhibition of interleukin-5 gene expression by dexamethasone. , 1992, Immunology.

[33]  S. Ben‐Sasson,et al.  Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation , 1992, The Journal of cell biology.

[34]  S. Durham,et al.  Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. , 1992, The American review of respiratory disease.

[35]  J. Bousquet,et al.  International consensus report on diagnosis and management of asthma , 1992, Allergy.

[36]  S. Durham,et al.  Application of monoclonal antibodies against major basic protein (BMK‐13) and eosinophil cationic protein (EG1 and EG2) for quantifying eosinophils in bronchial biopsies from atopic asthma , 1992, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[37]  S. Durham,et al.  Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. , 1992, The New England journal of medicine.

[38]  S. Korsmeyer,et al.  BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[39]  C. Reed.  Aerosol steroids as primary treatment of mild asthma. , 1991, The New England journal of medicine.

[40]  A J Wardlaw,et al.  Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. , 1991, The Journal of clinical investigation.

[41]  J. Bousquet,et al.  Eosinophilic inflammation in asthma. , 1990, The New England journal of medicine.

[42]  S. Holgate,et al.  Cellular events in the bronchi in mild asthma and after bronchial provocation. , 1989, The American review of respiratory disease.

[43]  A. Wardlaw,et al.  Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma. Relationship to bronchial hyperreactivity. , 1988, The American review of respiratory disease.

[44]  S. Hurd,et al.  Summary and recommendations of a workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in asthmatic patients. , 1985, Chest.

[45]  K Aas,et al.  Heterogeneity of Bronchial Asthma , 1981, Allergy.