The role of surfactant protein A in mycobacterial clearance

Surfactant protein A (SP-A) is a recently acknowledged participant of the pulmonary innate immune system. The structure of the protein consists of an N-terminal collagen-like domain, a hinge region, and a C-terminal carbohydrate recognition domain. Various in vitro and in vivo studies have demonstrated that this protein is capable of binding to the sugar moieties on the surfaces of microorganisms and presenting them to alveolar macrophages for phagocytosis. Thus, SP-A is potentially an important first line of defense against the establishment of infection in the lung.; The aim of these studies is to determine whether SP-A affects macrophage-mediated clearance of mycobacteria. Mycobacterium tuberculosis (Mtb) and Mycobacterium avium Complex (MAC) are two clinically important mycobacterial species that are capable of intracellular survival and subsequent chronic infection in the lung. These studies demonstrate that SP-A is able to enhance killing of Mycobacterium bovis bacillus Calmette-Guerin (BCG) via a nitric oxide (NO)-dependent pathway. SP-A is able to bind to MAC and enhance its ingestion by rat bone marrow-derived macrophages (RBMM). However, SP-A does not affect the macrophage-mediated killing of MAC.; Activation of signaling pathways is also examined to investigate the intracellular mechanisms by which SP-A enhances macrophage-mediated BCG clearance. Inhibition of tyrosine kinases decreases SP-A-mediated NO production and BCG killing. Treatment of RBMM with BCG-SP-A leads to greater phosphorylation and activation of extracellular signal-related kinases 1 and 2 (Erk-1/2) compared to RBMM infected with BCG alone. Further, inhibition of the upstream kinases of Erk-1/2 lead to a reduction in BCG-SP-A-mediated NO production.; These studies demonstrate that SP-A has roles in promoting mycobacterial clearance and survival, depending on the specific mycobacterial species and activation of signaling cascades. These findings provide more insight into the many functions of SP-A as a participant in pulmonary innate immunity.