EARLY INHIBITION OF MYCOBACTERIAL GROWTH BY HUMAN ALVEOLAR MACROPHAGES IS NOT DUE TO NITRIC-OXIDE

Phagocytic cells provide the first line of defense against mycobacteri a. We examined the relative mycobacteriostatic contributions of normal human alveolar macrophages (HAM), peripheral blood monocytes (PBM), a nd polymorphonuclear leukocytes (PMN) in the early time period after i nfection with mycobacteria (48 h). Cells were infected with Mycobacter ium bovis (BCG) or M. tuberculosis H37Ra and their ability to inhibit growth was determined by mycobacterial incorporation of [H-3]uracil. H AM inhibited the growth of both mycobacteria (44.2 +/- 7.9 and 37.6 +/ - 10.5% inhibition, respectively). Two populations of HAM donors were subsequently defined: inhibitors and noninhibitors. The ability to inh ibit growth of H37Ra correlated with that of BCC. In contrast to HAM, PBM and PMN did not inhibit mycobacterial growth. Because nitric oxide (NO) has been proposed to mediate growth inhibition in murine models, we examined whether NO was responsible for the early growth inhibitio n of mycobacteria by HAM. As expected, in murine peritoneal macrophage s (MPM) IFN-gamma (2,500 U/ml) enhanced growth inhibition of BCC; the effect was abolished by the nitric oxide synthase (NOS) inhibitor NMMA . In contrast, IFN-gamma failed to enhance growth inhibition by HAM or PBM and NMMA had no effect. MPM expressed inducible nitric oxide synt hase (NOS2) mRNA in response to LPS and IFN-gamma and produced NO. Nei ther NOS2 mRNA nor NO could be detected in HAM stimulated with LPS and IFN-gamma or mycobacteria. These data demonstrate that HAM, but not P BM or PMN, have NO-independent mycobacteriostatic activity in the earl y time period after infection with mycobacteria.