Low density lipoprotein- and high density lipoprotein-mediated signal transduction and exocytosis in alveolar type II cells.
Low density lipoproteins (LDL) and high density lipoproteins (HDL) from serum stimulate signal-transduction pathways and exocytosis in rat alveolar type II cells. Both LDL and HDL stimulated primary cultures of type II cells to secrete phosphatidylcholine (PtdCho), the major phospholipid component of pulmonary surfactant. The effects on secretion were preceded temporally by stimulation of inositol phospholipid catabolism, 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 LDL on signal transduction and PtdCho secretion but did not inhibit the effects of HDL. Unilamellar PtdCho liposomes the size of native LDL had no effect on type II cells; however, PtdCho complexes containing either 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, type II cells exhibited two major bands of 130 kDa and 120 kDa and a minor band at 230 kDa that also was present under reducing conditions. These results are consistent with our hypothesis that the LDL-receptor pathway functions in vivo to deliver cholesterol to type II cells and that this process is coupled to surfactant assembly and secretion via signal-transduction pathway(s). HDL elicits similar responses independent of the LDL receptor, suggesting that type II cells may use the selective uptake pathway to obtain cholesterol or that HDL triggers signal transduction by mechanisms unrelated to lipid delivery.
Voyno-Yasenetskaya
T A
TA
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Dobbs
L G
LG
Erickson
S K
SK
Hamilton
R L
RL
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005089:Exocytosis; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011973:Receptors, LDL / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D007295:Inositol Phosphates; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010716:Phosphatidylinositols; D011973:Receptors, LDL; D000255:Adenosine Triphosphate; D006493:Heparin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium