Induction of T-kininogen and tumor necrosis factor-alpha by macrophage migration inhibitory factor in vivo.
Administration of lipopolysaccharide (LPS) induces inflammation and tissue injuries that occasionally results in disseminated intravascular coagulation (DIC). This process is believed to be mediated by vasoactive molecules such as kinins and leads to endothelial damage and obstruction of the microcirculation. In this study, we evaluated the involvement of T-kininogen and macrophage migration inhibitory factor (MIF) in endotoxin-induced systemic inflammation. T-Kininogen is a protein unique to the rat and known as an acute-phase protein in response to endotoxins. Similarly, MIF functions as a proinflammatory cytokine and glucocorticoid-induced immunoregulator. First, we examined the effects of anti-MIF antibody on Wistar King male rats (ca 400 g) treated with intraperitoneal injection of LPS. At 6 hours after LPS injection (5 mg/kg), the platelet counts had decreased from 85 +/- 12.8 (x 10(4)/microL) to 8.8 +/- 2.6 (x 10(4)/microL). We treated these rats with the anti-rat MIF antibody (5 mg gamma G immunoglobulin [IgG] fraction/kg) 2 hours prior to LPS injection. This treatment prevented the decrease in platelet counts (45.6 +/- 5.6 [x 10(4)/microL]). Next, we examined the potential of MIF for production of T-kininogen. Intraperitoneal injection of rat MIF significantly upregulated the serum content of T-kininogen at the dose of 500 microg MIF/head. These results imply that MIF and T-kininogen might function in concert in the event of endotoxin-induced inflammation.
Nishihira
J
J
Central Research Institute, Hokkaido University School of Medicine, Sapporo, Japan. j_nisihi@med.hokudai.ac.jp
Mizue
Y
Y
Sakamoto
W
W
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D007704:Kininogens / Q000096:biosynthesis* / Q000097:blood / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects
D000906:Antibodies; D007704:Kininogens; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha