Surfactant protein A enhances apoptotic cell uptake and TGF- 1 release by inflammatory alveolar macrophages

Reidy, Michael F., and Jo Rae Wright. Surfactant protein A enhances apoptotic cell uptake and TGF1 release by inflammatory alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 285: L854–L861, 2003. First published June 6, 2003; 10.1152/ajplung.00439.2002.—The phagocytosis of apoptotic inflammatory cells by alveolar macrophages (AMs) is a key component of inflammation resolution within the air space. Surfactant protein A (SP-A) has been shown to stimulate the phagocytosis of apoptotic neutrophils (PMNs) by normal AMs. We hypothesized that SP-A promotes the resolution of alveolar inflammation by enhancing apoptotic PMN phagocytosis and anti-inflammatory cytokine release by inflammatory AMs. Using an LPS lung inflammation model, we determined that SP-A stimulates the phagocytosis of apoptotic PMNs threefold by normal AMs and AMs isolated after LPS injury. Furthermore, SP-A enhances transforming growth factor1 (TGF1) release from both AM populations. Inflammatory AMs release twofold more TGF1 in culture than do normal AMs. SP-A and apoptotic PMNs together stimulate TGF1 release equivalently from normal and inflammatory cultured AMs (330% of unstimulated release by normal AMs). In summary, SP-A enhances apoptotic PMN uptake, stimulates AM TGF1 release, and modulates the amount of TGF1 released when AMs phagocytose apoptotic PMNs. These findings support the hypothesis that SP-A promotes the resolution of alveolar inflammation.