Surfactant protein A suppresses reactive nitrogen intermediates by alveolar macrophages in response to Mycobacterium tuberculosis

Mycobacterium tuberculosis attaches to, enters, and replicates within alveo lar macrophages (AMs). Our previous studies suggest that surfactant protein A (SP-A) can act as a ligand in the attachment of M. tuberculosis to AMs. Reactive nitrogen intermediates (RNIs) pray a significant role in the killi ng of mycobacteria. We have demonstrated that RNI levels generated by AMs w ere significantly increased when interferon-gamma-primed AMs were incubated with M, tuberculosis. However, the RNI levels were significantly suppresse d in the presence of SP-A (10 mu g/ml). The specificity of SP-A's effect wa s demonstrated by the use of F(ab')(2) fragments of anti-SP-A monoclonal an tibodies and by the use of mannosyl-BSA, which blocked the suppression of R NI levels by SP-A. Furthermore, incubation of deglycosylated SP-A with M. t uberculosis failed to suppress RNI by AMs, suggesting that the oligosacchar ide component of SP-A, which binds to M. tuberculosis, is necessary for thi s effect. These results show that SP-A-mediated binding of M. tuberculosis to AMs significantly decreased RNI levels, suggesting that this may be one mechanism by which M. tuberculosis diminishes the cytotoxic response of act ivated AMs.