title: Surfactant protein A enhances Mycobacterium avium ingestion but not killing by rat macrophages.
abstract: Mycobacterium avium complex (MAC) is a significant cause of opportunistic infection in patients with acquired immunodeficiency syndrome. Although the major route of entry of MAC is via the gastrointestinal tract, MAC can infect humans through the respiratory tract and eventually encounter alveolar macrophages within the lung. Once in the lung, MAC can potentially interact with surfactant protein A (SP-A), an important component of the pulmonary innate-immune response. Previous work on other pulmonary pathogens including Mycobacterium bovis Bacillus Calmette-Guerin (BCG) suggests that SP-A participates in promoting efficient clearance of these organisms by alveolar macrophages. In the present study, we investigated the role of SP-A in clearance of MAC by cultured rat macrophages. SP-A bound to MAC organisms and enhanced the ingestion of the mycobacteria by macrophages. Infection of macrophages with SP-A-MAC complexes induced the production of nitric oxide (NO) and tumor necrosis factor-alpha. However, intracellular survival of MAC was not altered by preopsonization with SP-A. In addition, inhibitors of inducible NO synthase did not alter MAC clearance. These results suggest that SP-A can bind to and enhance the uptake of MAC by alveolar macrophages, similar to previous findings with BCG and Mycobacterium tuberculosis.However, unlike BCG and other pulmonary pathogens that are cleared effectively in the presence of SP-A via a NO-dependent pathway, macrophage-mediated clearance of MAC is not enhanced by SP-A.
authors.affiliation: Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Lopez
authors.forename: Emily
authors.initials: E
authors.lastname: Clark
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Shepherd
mesh_terms: D000818:Animals; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D015269:Mycobacterium avium Complex / Q000276:immunology*; D009569:Nitric Oxide / Q000502:physiology; D010587:Phagocytosis; D037662:Pulmonary Surfactant-Associated Protein A / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide