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.
View: Text | PDF
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

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Effect of IFN-γ alone and IFN-γ and M. tuberculosis on RNI production by...
Effect of IFN-γ alone and IFN-γ and M. tuberculosis on RNI production by AMs. AMs were stimulated with increasing concentrations of IFN-γ alone (0–1,000 U/ml) for 48 h or with IFN-γ for 48 h with the addition of M. tuberculosis after 24 h IFN-γ preincubation. After incubation, the amount of RNI present in the supernatants was determined by IFN-γ alone and was minimal in comparison to the RNI produced by IFN-γ–stimulated AMs in the presence of M. tuberculosis infection. The production of RNI occurred in a concentration-dependent manner, reaching a maximum at 100 U IFN-γ/ml. Results are expressed as mean ± SEM of three experiments performed in triplicate. AMs, alveolar macrophages; IFN-γ, interferon-γ; MTB, M. tuberculosis; RNI, reactive nitrogen intermediates.