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 liver macrophages cytotoxicity against tumor target cells and a release of TNF-alpha, nitric oxide, and eicosanoids but not a generation of superoxide anions. Neither agent elicits a formation of inositol phosphates, a change in intracellular free calcium, or a translation of protein kinase C-beta. Inhibition or down-regulation of protein kinase C does not inhibit the release of TNF-alpha and nitric oxide but inhibits the formation of prostanoids. In contrast to LPS, liposome -encapsulated MTP-PE induces an elevation of diacylglycerol mass and an enhanced expression of protein kinase C-delta. LPS, but not liposome-encapsulated MTP-PE, elicits an enhanced expression of cytosolic phospholipase A2 and a predominant formation of PGE2. Both agents elicit different responses when given to cells pretreated with one of the immunomodulators, with dexamethasone, or with PGE2. In contrast, to liposome-encapsulated MTP-PE, LPS induces only cytotoxicity when added to liver macrophages simultaneously or a maximum of 2 h before the addition of tumor target cells. The observed differences might reflect partly differences in the potencies of LPS and some liposome-encapsulated MTP-PE as immunomodulators.
Dieter
P
P
Biochemical Institute, University of Freiburg, Germany.
Ambs
P
P
Fitzke
E
E
Hidaka
H
H
Hoffmann
R
R
Schwende
H
H
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D015232:Dinoprostone / Q000096:biosynthesis; D004337:Drug Carriers; D015777:Eicosanoids / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008081:Liposomes; D008099:Liver / Q000166:cytology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004337:Drug Carriers; D015777:Eicosanoids; D008070:Lipopolysaccharides; D008081:Liposomes; D010714:Phosphatidylethanolamines; D014409:Tumor Necrosis Factor-alpha; C037144:mifamurtide; D009569:Nitric Oxide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D015232:Dinoprostone