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

Laura F. Weikert, Joseph P. Lopez, Rasul Abdolrasulnia, Zissis Chroneos, Virginia L. Shepherd

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

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 languageEnglish (US)
Pages (from-to)L216-L223
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume279
Issue number2 23-2
DOIs
StatePublished - 2000

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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