Abstract
Surfactant-associated protein A (SP-A) is involved in surfactant homeostasis arid 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 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-α (TNF-α) and nitric oxide were measured at varying times. TNF-α 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.
Original language | English (US) |
---|---|
Pages (from-to) | L216-L223 |
Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
Volume | 279 |
Issue number | 2 23-2 |
DOIs | |
State | Published - 2000 |
All Science Journal Classification (ASJC) codes
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology