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.