LOW-DENSITY LIPOPROTEIN-MEDIATED AND HIGH-DENSITY LIPOPROTEIN-MEDIATED SIGNAL TRANSDUCTION AND EXOCYTOSIS IN ALVEOLAR TYPE-II CELLS

Low density lipoproteins (LDL) and high density lipoproteins (HDL) fro m serum stimulate signal-transduction pathways and exocytosis in rat a lveolar type II cells. Both LDL and HDL stimulated primary cultures of type II cells to secrete phosphatidylcholine (PtdCho), the major phos pholipid component of pulmonary surfactant. The effects on secretion w ere preceded temporally by stimulation of inositol phospholipid catabo lism, calcium mobilization, and translocation of protein kinase C from cytosolic to membrane compartments. Heparin, which blocks the binding of ligands to the LDL receptor, completely inhibited the effects of L DL on signal transduction and PtdCho secretion but did not inhibit the effects of HDL. Unilamellar PtdCho liposomes the size of native LDL h ad no effect on type II cells; however, PtdCho complexes containing ei ther apolipoproteins E or A-I stimulated both signal transduction and PtdCho secretion. LDL receptors were present in type II cell membranes by immunoblotting. In contrast to findings with hepatic membranes, ty pe II cells exhibited two major bands of 130 kDa and 120 kDa and a min or band at 230 kDa that also was present under reducing conditions. Th ese results are consistent with our hypothesis that the LDL-receptor p athway functions in vivo to deliver cholesterol to type II cells and t hat this process is coupled to surfactant assembly and secretion via s ignal-transduction pathway(s). HDL elicits similar responses independe nt of the LDL receptor, suggesting that type II cells may use the sele ctive uptake pathway to obtain cholesterol or that HDL triggers signal transduction by mechanisms unrelated to lipid delivery.