Stimulation of glycogen phosphorylase in rat hepatocytes via prostanoid release from Kupffer cells by recombinant rat anaphylatoxin C5a but not by native human C5a in hepatocyte/Kupffer cell co-cultures.
Human anaphylatoxin C3a had previously been shown to increase glycogenolysis in perfused rat liver and prostanoid formation in rat liver macrophages. Surprisingly, human C5a, which in other systems elicited stronger responses than C3a, did not increase glycogenolysis in perfused rat liver. Species incompatibilities within the experimental system had been supposed to be the reason. The current study supports this hypothesis: (1) In rat liver macrophages that had been maintained in primary culture for 72 h recombinant rat anaphylatoxin C5a in concentrations between 0.1 and 10 micrograms/ml increased the formation of thromboxane A2, prostaglandin D2, E2 and F2 alpha 6- to 12-fold over basal within 10 min. In contrast, human anaphylatoxin C5a did not increase prostanoid formation in rat Kupffer cells. (2) The increase in prostanoid formation by recombinant rat C5a was specific. It was inhibited by a neutralizing monoclonal antibody. (3) In co-cultures of rat hepatocytes and rat Kupffer cells but not in hepatocyte mono-cultures recombinant rat C5a increased glycogen phosphorylase activity 3-fold over basal. This effect was inhibited by incubation of the co-cultures with 500 microM acetylsalicyclic acid. Thus, C5a generated either locally in the liver or systemically e.g. in the course of sepsis, may increase hepatic glycogenolysis by a prostanoid-mediated intercellular communication between Kupffer cells and hepatocytes.
Hespeling
U
U
Institut für Biochemie und Molekulare Zellbiologie, George-August-Universität, Göttingen, Germany.
Püschel
G P
GP
Jungermann
K
K
Götze
O
O
Zwirner
J
J
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015936:Complement C5a / Q000235:genetics / Q000494:pharmacology*; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D006005:Phosphorylases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D011453:Prostaglandins; D011994:Recombinant Proteins; D013929:Thromboxane B2; D013928:Thromboxane A2; D015936:Complement C5a; D006005:Phosphorylases; D000118:Acetylglucosaminidase; D001241:Aspirin; D009638:Norepinephrine