Surfactant protein A suppresses reactive nitrogen intermediates by alveolar macrophages in response to Mycobacterium tuberculosis
Rajamouli Pasula, … , Diane L. Kachel, William J. Martin II
Rajamouli Pasula, … , Diane L. Kachel, William J. Martin II
Published February 15, 1999
Citation Information: J Clin Invest. 1999;103(4):483-490. https://doi.org/10.1172/JCI2991.
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Article

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

Abstract

Mycobacterium tuberculosis attaches to, enters, and replicates within alveolar 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) play a significant role in the killing of mycobacteria. We have demonstrated that RNI levels generated by AMs were significantly increased when interferon-γ–primed AMs were incubated with M. tuberculosis. However, the RNI levels were significantly suppressed in the presence of SP-A (10 μg/ml). The specificity of SP-A's effect was demonstrated by the use of F(ab′)2 fragments of anti–SP-A monoclonal antibodies and by the use of mannosyl-BSA, which blocked the suppression of RNI levels by SP-A. Furthermore, incubation of deglycosylated SP-A with M. tuberculosis failed to suppress RNI by AMs, suggesting that the oligosaccharide component of SP-A, which binds to M. tuberculosis, is necessary for this 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 activated AMs.

Authors

Rajamouli Pasula, Jo Rae Wright, Diane L. Kachel, William J. Martin II

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Effect of SP-A on M. tuberculosis growth. Effect of SP-A on M. tuberculo...
Effect of SP-A on M. tuberculosis growth. Effect of SP-A on M. tuberculosis growth was determined by the BACTEC radiometric method. AMs were infected with M. tuberculosis at a ratio of 10:1 (M. tuberculosis:AM) in the presence of IFN-γ (100 U/ml), SP-A (5 μg/ml), or anti–SP-A antibodies (100 μg/ml). AMs were washed with DMEM to remove unbound M. tuberculosis organisms, and IFN-γ, SP-A, and SP-A antibodies were added back with the fresh medium for 24 h. The AMs were then lysed and inoculated into the BACTEC vials. The vials were then incubated at 37°C, with growth of M. tuberculosis being determined every 24 h by the BACTEC TB instrument. Preincubation of AMs and M. tuberculosis with SP-A significantly increased M. tuberculosis growth. These results suggest that blocking the effect of SP-A again restores the ability of AMs to inhibit the growth of M. tuberculosis.