title: Comparison of the immunopathology of extrinsic, intrinsic and occupational asthma.
abstract: Using immunohistochemistry and a panel of monoclonal antibodies we have compared T lymphocyte, eosinophil, macrophage and neutrophil infiltration and expression of adhesion receptors (ICAM-1, E-selectin and VCAM-1) in bronchial biopsies from 10 intrinsic asthmatics, 9 isocyanate-induced asthmatics, 10 extrinsic asthmatics and 12 normal healthy nonatopic controls. There was a significant increase in the number of CD25+ (interleukin-2 receptor [IL-2R]-bearing) cells (p < 0.01) in isocyanate-induced asthma compared with that of controls. There were also significant increases in MBP+ cells (p < 0.02) and EG2+ cells (p < 0.01), which represent total and activated eosinophils. CD25+ (p < 0.01), MBP+ (p < 0.03) and EG2+ (p < 0.01) cells were also elevated in extrinsic asthma. An intense mononuclear cell infiltrate was identified in intrinsic asthmatics with an increase in the number of CD45+ cells (total leukocytes), CD3+ and CD4+ T lymphocytes and CD68+ macrophages (p < 0.03, p < 0.01, p < 0.03 and p < 0.03, respectively), compared with normal controls. CD25+ cells (IL-2R+) and the number of MBP+ and actively secreting eosinophils were also increased in intrinsic asthmatics compared with normal controls (p < 0.01, p < 0.01 and p < 0.01, respectively). EG2+ cell numbers in intrinsic asthma correlated with the Aas symptom score (r = 0.65, p < 0.05), where EG2+ cell numbers in intrinsic and extrinsic asthmatics correlated with airways methacholine responsiveness (r = -0.5, p < 0.03) and the Aas symptom score (r = 0.54, p < 0.03). There was constitutive expression of ICAM-1, E-selectin and VCAM-1 in patients with asthma (intrinsic and extrinsic) and normal controls. Compared with controls, ICAM-1 and E-selectin staining in the submucosa was increased in intrinsic asthma both for intensity (p < 0.02, p < 0.05) and extent of staining (p < 0.01, p < 0.05). Epithelial expression of ICAM-1 was more frequent in asthmatics than control subjects (p < 0.05). These results suggest that T cell activation and eosinophil infiltration are features common to asthma of diverse etiology. There appears to be a complex pattern in in vivo of regulation for ICAM-1, E-selectin and VCAM-1, where they may reflect the degree of ongoing inflammation in asthma.
authors.affiliation: Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Bentley
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: A B
authors.initials: AB
authors.lastname: Kay
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D001249:Asthma / Q000145:classification / Q000276:immunology* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017953:Isocyanates / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000276:immunology / Q000473:pathology; D012129:Respiratory Function Tests; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D017953:Isocyanates