Modifications of experimental bronchopulmonary hyperresponsiveness.
Bronchopulmonary hyperresponsiveness (BHR) is a hallmark of asthma and other inflammatory diseases of the airways. Animal models of BHR are available in which systemic or local immunizations, followed by acute allergenic provocations into the airways, augment responses to intravenous or intratracheal nonspecific bronchoconstrictor agents. Guinea-pig models are easy to manipulate but have serious handicaps: lack of proper genetics, lack of biomolecular tools, and frequent excess of eosinophils in the bronchoalveolar lavage fluid (BALF). Murine models have proper genetics and molecular tools, and they have the further advantage of being widely used for the study of other pathologies. In many of these studies, interleukin (IL)-5 appears as a major cytokine, produced by Th2 lymphocytes. Interleukin-5 promotes eosinophil differentiation and maturation, recruitment to the airways, and possibly activation. The presence of eosinophils in the airways and in the BALF may be necessary but is not sufficient to support BHR, since intense eosinophilia may be present in its absence. Bronchopulmonary hyperresponsiveness is also induced by the administration of lipopolysaccharide (LPS); in that case, eosinophils are not involved, and the role of neutrophils and of tumor necrosis factor-alpha, even though likely, has not been proven. Comparison of BHR induced by allergen (Th2- and largely eosinophil-dependent) and by LPS (probably macrophage-dependent) should allow for a better understanding of the mechanisms of BHR and for the development of important remedies.
Vargaftig
B B
BB
Unité de Pharmacologie Cellulaire, Institut Pasteur, Paris, France.
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D007111:Immunity, Cellular; D008070:Lipopolysaccharides / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity
D008070:Lipopolysaccharides