PATHOGENIC ROLES OF THE ALVEOLAR MACROPHAGE IN ASTHMA

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Asthma is a disease of great clinical and economic importance, afflicting some nine million young, otherwise healthy individuals. Inflammation is an important aspect of asthma, but many potential determinants of inflammation have not been studied. Roles of the alveolar macrophage (AM) will be determined by these proposed studies. It is likely that these cells contribute to airway inflammation and hyperreactivity by generation of high energy oxygen species (HEOS), release of chemotactins for inflammatory cells such as eosinophils and neutrophils, and elaboration of factors promoting histamine release. Allergic asthmatic subjects will be studied before and after bronchoprovaction (BP) with antigen to which they are sensitive, and AM recovered by bronchoalveolar lavage. HEOS metabolism will be established by biochemical determinations of superoxide and hydrogen peroxide in addition to luminol-enhanced chemiluminescence response. Release of chemotactins for granulocytes will be determined by standard microchemotaxis assays, and AM-derived histamine releasing activity by fluorimetric analysis of histamine. Results from allergic asthma patients after BP will be compared to those obtained from normal controls and allergic rhinitis patients, and to their own values prior to BP.