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 concentrations on RNI production by IFN-γ–stimulated AMs ...
Effect of SP-A concentrations on RNI production by IFN-γ–stimulated AMs in the presence and absence of M. tuberculosis. AMs were stimulated with IFN-γ (100 U/ml) for 48 h in the presence of increasing concentrations of exogenous human SP-A (0–40 μg/ml) at 37°C. Additional AMs were stimulated with IFN-γ for 24 h in the presence of increasing concentrations of exogenous human SP-A (0–40 μg/ml) at 37°C and then infected with M. tuberculosis for an additional 24 h. After incubation, the supernatants were collected and RNI levels were determined. The results indicate that concentrations of SP-A up to 20 μg/ml significantly decreased nitrite production by IFN-γ–stimulated AMs infected with M. tuberculosis. Results are expressed as mean ± SEM of three experiments performed in triplicate. SP-A, surfactant protein A.