Involvement of inflammatory leukocytes in hepatic induction of T-kininogen in rat

Hepatic synthesis as well as plasma levels of T-kininogen, a protein precursor of T-kinin (Ile-Ser-bradykinin), increase in rats following the induction of acute inflammation. Studies have been undertaken to elucidate an involvement of inflammatory leukocytes in the acute-phase response of T-kininogen. Peritoneal exudate cells (PEC) were prepared from rats six days after the intraperitoneal injection of Freund's complete adjuvant. By transfer of these leukocytes into the peritoneal cavity of normal rats, plasma kininogen levels of these recipients increased about threefold after one day. Secretion of kininogen from rat hepatocytes in primary culture was enhanced about twofold by coculturing with PEC. A similar effect was also obtained by adding culture supernatant of these leukocytes into hepatocytes, and the increased levels of kininogen in culture medium of hepatocytes was due to the increased levels of T-kininogen. From these results, it was concluded that leukocytes in the inflammatory site, probably macrophages, release some substance(s) which stimulate(s) the hepatic synthesis of T-kininogen.This study was supported in part by a Grant-in-Aid from the Naito Foundation and one (No. 61580154) from the Ministry of Education, Science and Culture of Japan.