INCREASED PRODUCTION OF HYDROGEN-PEROXIDE AND EXPRESSION OF CD11B CD18 ON ALVEOLAR MACROPHAGES IN PATIENTS WITH ACTIVE PULMONARY TUBERCULOSIS/

Setting: Alveolar macrophages (AM) are important in host defense again st Mycobacterium tuberculosis (TB). beta 2-integrins, especially CD11a /CD18 and CD11b/CD18, are implicated in leukocyte migration, antigen p resentation, phagocytosis, and production of reactive oxygen species O bjective: To explore the functional relevance of beta 2-integrin expre ssion to intracellular H2O2 capacity of AM in TB patients. Design: In a prospective study, AM retrieved from 18 active pulmonary TB patients and 18 normal subjects were assessed for beta(2)-integrin expression and intracellular H2O2 metabolism capacity by loading with anti-CD11la /CD18, anti-CD11b/CD18 monoclonal antibodies and 2',7' dichlorofluores cein diacetate (DCFH;DA) respectively, and analyzed by flow cytometry. AM from 8 normal subjects were stimulated with tumor necrosis factor- alpha (TNF-alpha, 10(5) units/ml) to examine the relationship between H2O2 production and CD11b/CD18 expression. Results: The magnitude of D CFH oxidation and CD11b/CD18 expression of AM was higher in TB patient s than in normal subjects. The CD11b/CD18 expression was related to th e magnitude of DCFH oxidation, but not to lymphocyte numbers or subpop ulations (CD4, CD8, CD25). Stimulation of AM with TNF-alpha increased H2O2 production and CD11b/CD18 expression. Pretreatment with CD11b/CD1 8 monoclonal antibodies inhibited TNF-alpha-induced H2O2. Conclusion: AM in TB patients possessed a higher capacity of oxidant metabolism. T he increased CD11b/CD18 expression may be related to the increased res piratory burst response in AM against mycobacterial invasion.