Surfactant protein A enhances mycobacterial killing by rat macrophages through a nitric oxide-dependent pathway

Laura F. Weikert, Joseph P. Lopez, Rasul Abdolrasulnia, Zissis C. Chroneos, Virginia L. Shepherd
2000 American Journal of Physiology - Lung cellular and Molecular Physiology  
Surfactant protein A enhances mycobacterial killing by rat macrophages through a nitric oxide-dependent pathway. Am J Physiol Lung Cell Mol Physiol 279: L216-L223, 2000.-Surfactant-associated protein A (SP-A) is involved in surfactant homeostasis and host defense in the lung. We have previously demonstrated that SP-A specifically binds to and enhances the ingestion of bacillus Calmette-Guerin (BCG) organisms by macrophages. In the current study, we investigated the effect of SP-A on the
more » ... SP-A on the generation of inflammatory mediators induced by BCG and the subsequent fate of ingested BCG organisms. Rat macrophages were incubated with BCG in the presence and absence of SP-A. Noningested BCG organisms were removed, and the release of tumor necrosis factor-␣ (TNF-␣) and nitric oxide were measured at varying times. TNF-␣ and nitric oxide production induced by BCG were enhanced by SP-A. In addition, SP-A enhanced the BCG-induced increase in the level of inducible nitric oxide synthase protein. Addition of antibodies directed against SPR210, a specific macrophage SP-A receptor, inhibited the SP-A-enhanced mediator production. BCG in the absence of SP-A showed increased growth over a 5-day period, whereas inclusion of SP-A dramatically inhibited BCG growth. Inhibition of nitric oxide production blocked BCG killing in the presence and absence of SP-A. These results demonstrate that ingestion of SP-A-BCG complexes by rat macrophages leads to production of inflammatory mediators and increased mycobacterial killing. phagocytosis; mycobacteria; surfactant-associated protein A
doi:10.1152/ajplung.2000.279.2.l216 pmid:10926544 fatcat:jj6d6atvizftfdqdj7qscgon5e