Increase of glucose and lactate output and decrease of flow by human anaphylatoxin C3a but not C5a in perfused rat liver.
The complement fragments C3a and C5a were purified from zymosan-activated human serum by column chromatographic procedures after the bulk of the proteins had been removed by acidic polyethylene glycol precipitation. In the isolated in situ perfused rat liver C3a increased glucose and lactate output and reduced flow. Its effects were enhanced in the presence of the carboxypeptidase inhibitor DL-mercaptomethyl-3-guanidinoethylthio-propanoic acid (MERGETPA) and abolished by preincubation of the anaphylatoxin with carboxypeptidase B or with Fab fragments of an anti-C3a monoclonal antibody. The C3a effects were partially inhibited by the thromboxane antagonist BM13505. C5a had no effect. It is concluded that locally but not systemically produced C3a may play an important role in the regulation of local metabolism and hemodynamics during inflammatory processes in the liver.
Püschel
G P
GP
Institut für Biochemie, Georg-August-Universität, Göttingen, FRG.
Oppermann
M
M
Muschol
W
W
Götze
O
O
Jungermann
K
K
D000706:Anaphylatoxins / Q000494:pharmacology*; D000818:Animals; D003176:Complement C3 / Q000276:immunology* / Q000302:isolation & purification; D015926:Complement C3a; D003182:Complement C5 / Q000276:immunology* / Q000302:isolation & purification; D015936:Complement C5a; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D007773:Lactates / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000706:Anaphylatoxins; D003176:Complement C3; D003182:Complement C5; D007773:Lactates; D010455:Peptides; D015926:Complement C3a; D015936:Complement C5a; D005947:Glucose