Natural protection from apoptosis by surfactant protein A in type II pneumocytes

Surfactant-associated protein A (SP-A) is a component of pulmonary surfacta nt that binds to a specific receptor (SPAR) on the surface of type II alveo lar cells of the lung and regulates gene expression and surfactant secretio n. Previously we have shown that activation of SPAR by SP-A binding initiat es a signal through pathways that involve tyrosine phosphorylation, include IRS-1, and entail activation of phosphatidylinositol 3-kinase (PI3K). In o ther cell types, cytokines that activate the PI3K signaling pathway promote cell survival. Therefore we investigated whether there was an effect of SP -A on apoptosis as measured by DNA laddering, FAGS analysis, TUNEL assay, a nd annexin V binding. SP-A protected primary cultures of rat type II alveol ar cells against the apoptotic effects of etoposide and UV light and also p rotected the H441 human Clara lung tumor cell line against staurosporine-in duced apoptosis. The protective effects of SP-A were abrogated by inhibitio n of either tyrosine-specific protein kinase activity or PI3K. SP-A/SPAR in teraction thus initiates a signaling pathway that regulates apoptosis in ty pe II cells. These findings may be important in understanding the pathogene sis of acute lung injury and pulmonary tumorigenesis and may suggest new th erapeutic options. (C) 2001 Academic Press.