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 against Mycobacterium tuberculosis (TB). beta 2-integrins, especially CD11a/CD18 and CD11b/CD18, are implicated in leukocyte migration, antigen presentation, phagocytosis, and production of reactive oxygen species.

OBJECTIVE

To explore the functional relevance of beta 2-integrin expression 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-CD11a/CD18, anti-CD11b/CD18 monoclonal antibodies and 2',7' dichlorofluorescein 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 DCFH oxidation and CD11b/CD18 expression of AM was higher in TB patients than in normal subjects. The CD11b/CD18 expression was related to the magnitude of DCFH oxidation, but not to lymphocyte numbers or subpopulations (CD4, CD8, CD25). Stimulation of AM with TNF-alpha increased H2O2 production and CD11b/CD18 expression. Pretreatment with CD11b/CD18 monoclonal antibodies inhibited TNF-alpha-induced H2O2.

CONCLUSION

AM in TB patients possessed a higher capacity of oxidant metabolism. The increased CD11b/CD18 expression may be related to the increased respiratory burst response in AM against mycobacterial invasion.