Gp. Puschel et al., INCREASE IN PROSTANOID FORMATION IN RAT-LIVER MACROPHAGES (KUPFFER CELLS) BY HUMAN ANAPHYLATOXIN C3A, Hepatology, 18(6), 1993, pp. 1516-1521
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.