INCREASE IN PROSTANOID FORMATION IN RAT-LIVER MACROPHAGES (KUPFFER CELLS) BY HUMAN ANAPHYLATOXIN C3A

Human anaphylatoxin C3a increases glycogenolysis in perfused rat liver . This action is inhibited by prostanoid synthesis inhibitors and pros tanoid antagonists. Because prostanoids but not anaphylatoxin C3a can increase glycogenolysis in hepatocytes, it has been proposed that pros tanoid formation in nonparenchymal cells represents an important step in the C3a-dependent increase in hepatic glycogenolysis. This study sh ows that (a) human anaphylatoxin C3a (0.1 to 10 mug/ml) dose-dependent ly increased prostaglandin D2, thromboxane B, and prostaglandin F2alph a formation in rat liver macrophages (Kupffer cells); (b) the C3a-medi ated increase in prostanoid formation was maximal after 2 min and show ed tachyphylaxis; and (c) the C3a-elicited prostanoid formation could be inhibited specifically by preincubation of C3a with carboxypeptidas e B to remove the essential C-terminal arginine or by preincubation of C3a with Fab fragments of a neutralizing monoclonal antibody. These d ata support the hypothesis that the C3a-dependent activation of hepati c glycogenolysis is mediated by way of a C3a-induced prostanoid produc tion in Kupffer cells.