COMPARATIVE-STUDIES OF CYTOTOXICITY AND THE RELEASE OF TNF-ALPHA, NITRIC-OXIDE, AND EICOSANOIDS OF LIVER MACROPHAGES TREATED WITH LIPOPOLYSACCHARIDE AND LIPOSOME-ENCAPSULATED MTP-PE

LPS and liposome-encapsulated MTP-PE induce in liver macrophages cytot oxicity against tumor target cells and a release of TNF-alpha, nitric oxide, and eicosanoids but not a generation of superoxide anions. Neit her agent elicits a formation of inositol phosphates, a change in intr acellular free calcium, or a translocation of protein kinase C-beta. I nhibition or down-regulation of protein kinase C does not inhibit the release of TNF-alpha and nitric oxide but inhibits the formation of pr ostanoids. In contrast to LPS, liposome-encapsulated MTP-PE induces an elevation of diacylglycerol mass and an enhanced expression of protei n kinase C-delta. LPS, but not liposome-encapsulated MTP-PE, elicits a n enhanced expression of cytosolic phospholipase A(2) and a predominan t formation of PGE(2). Both agents elicit different responses when giv en to cells pretreated with one of the immunomodulators, with dexameth asone, or with PGE(2). In contrast to liposome-encapsulated MTP-PE, LP S induces only cytotoxicity when added to liver macrophages simultaneo usly or a maximum of 2 h before the addition of tumor target cells. Th e observed differences might reflect partly differences in the potenci es of LPS and liposome-encapsulated MTP-PE as immunomodulators.