2 INTRACELLULAR SIGNALING PATHWAYS FOR ACTIVATION OF PROTEIN-KINASE-CARE INVOLVED IN OXIDIZED LOW-DENSITY LIPOPROTEIN-INDUCED MACROPHAGE GROWTH

Recent studies demonstrated that oxidized LDL (Ox-LDL) induces macroph age growth in vitro. The present study was undertaken to elucidate the intracellular signaling pathways far macrophage growth. Ox-LDL initia ted a rapid and transient rise in intracellular free calcium ion and i nduced activation of membrane protein kinase C (PKC). Pertussis toxin completely inhibited the Ox-LDL-induced rise in free calcium ion and s ignificantly inhibited macrophage growth by 50%. Moreover, PKC inhibit ors calphostin C and H-7 significantly inhibited Ox-LDL-induced macrop hage growth by 80%. On the other hand, phospholipase A2-treated acetyl ated LDL did not induce a rise in calcium but significantly activated PKC and led to significant macrophage growth that was significantly in hibited by calphostin C by 90%. These results suggest the presence of two intracellular signaling pathways for activation of PKC, a rise in calcium that was mediated by pertussis toxin-sensitive G protein and t he internalization of lysophosphatidylcholine through the scavenger re ceptors. These two pathways may play an important role in Ox-LDL-induc ed macrophage growth.