Early inhibition of mycobacterial growth by human alveolar macrophages is not due to nitric oxide

C Aston, WN Rom, AT Talbot… - American journal of …, 1998 - atsjournals.org
C Aston, WN Rom, AT Talbot, J Reibman
American journal of respiratory and critical care medicine, 1998atsjournals.org
Phagocytic cells provide the first line of defense against mycobacteria. We examined the
relative mycobacteriostatic contributions of normal human alveolar macrophages (HAM),
peripheral blood monocytes (PBM), and polymorphonuclear leukocytes (PMN) in the early
time period after infection with mycobacteria (48 h). Cells were infected with Mycobacterium
bovis (BCG) or M. tuberculosis H37Ra and their ability to inhibit growth was determined by
mycobacterial incorporation of [3H] uracil. HAM inhibited the growth of both mycobacteria …
Phagocytic cells provide the first line of defense against mycobacteria. We examined the relative mycobacteriostatic contributions of normal human alveolar macrophages (HAM), peripheral blood monocytes (PBM), and polymorphonuclear leukocytes (PMN) in the early time period after infection with mycobacteria (48 h). Cells were infected with Mycobacterium bovis (BCG) or M. tuberculosis H37Ra and their ability to inhibit growth was determined by mycobacterial incorporation of [3H]uracil. HAM 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 inhibit growth of H37Ra correlated with that of BCG. 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 inhibition of mycobacteria by HAM. As expected, in murine peritoneal macrophages (MPM) IFN- γ (2,500 U / ml) enhanced growth inhibition of BCG; the effect was abolished by the nitric oxide synthase (NOS) inhibitor NMMA. In contrast, IFN- γ failed to enhance growth inhibition by HAM or PBM and NMMA had no effect. MPM expressed inducible nitric oxide synthase (NOS2) mRNA in response to LPS and IFN- γ and produced NO. Neither NOS2 mRNA nor NO could be detected in HAM stimulated with LPS and IFN- γ or mycobacteria. These data demonstrate that HAM, but not PBM or PMN, have NO-independent mycobacteriostatic activity in the early time period after infection with mycobacteria.
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