|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1997 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1996 : ¥1,000,000 (Direct Cost : ¥1,000,000)
In this study, complement and its regulatory system were investigated in the rat, human, and guinea pig gastrointestinal tract. Roles of complement and plasma carboxypeptidase (CP ; inactivator of C3a and C5a) in systemic shock following intestinal ischemia were studied using cobra venom factor (CVF,which reduced serum complement to undetectable level) and/or CP inhibitor. Pretreatment with CVF prevented, but CP inhibitor aggravated such a shock. In human gastric mucosa, DAF (membrane binding inhibitor of complement) was found to be unregulated during gastritis. The study on guinea pig gastric mucosa clearly demonstrated alternation in the expression of DAF gene and protein after gastric I/R.Expression of DAF mRNA was constitutively demonstrated in normal guinea pig gastric mucosa and was most intense in 6hr after I/R.However, it was detected at normal levels at 24 hr, 3 and 7 days. Expression of DAF protein was not significant from 0 to 12 hr after I/R but it was increased in amount at 24 hr and 3 days, returning to less than significant levels at 7 days. Expression of DAF isoform mRNA was also assessed by RT-PCR with specific primers for 6 isoforms (transmembrane types ; TM-a, TM-ab, TM-abc, and glycosylphosphatidyl-inositol anchored types ; GPI-a, GPI-ab, GPI-abc) were evaluated. Messenger RNAs for GPI-a, GPI-ab, GPI-abc, TM-a and TM-ab were constitutively detected in normal guinea pig gastric mucosa, whereas mRNA for TM-abc was not. However, 6 hr after I/R,mRNAs for TM-abc became detectable, with TM-a and TM-ab the dominant species. We also evaluated role of complement in a rat model for ischemia-induced gastric mucosal injury. Pretreatments with CVF and K-76 COOH,a inhibiter of complement action, significantly attenuated mucosal injury observed after reperfusion.
These findings support that complement and its regulatory system may play a significant role in pathology of gastrointestinal tract.