| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
|---|
| Research Abstract |
Neutrophils are the major inflammatory cells and involved in various inflammatory events. The neutrophil-dependent vascular permeability enhancement (VPE) is one of them, however, the mechanism has not been known. The VPE induced by neutrophil elastase (NE), a lysosomal enzyme released by inflammatory stimuli, was, therefore, investigated. NE produced VPE activity from human plasma, especially oxidized plasma and no VPE activity was produced from kininogen-deficient plasma. NE generated VPE activity from kininogens and the kininogen fragments were separated, being examined for VPE activity. Only a peptide, SLMKRPPGFSPFRSSRI, named as E-kinin, showed a VPE activity. VPE activity induced by E-kinin was comparable to that of bradykinin (BK) and sensitive to a BK B2-receptor antagonist. No rat uterus constriction was induced by E-kinin but E-kinin desSSRI, which has the same carboxy-terminal sequence as BK, exhibited the activity of 1/3 of BK activity. Both peptides lowered rat blood pressure in a BK B2-receptor-dependent manner. These results indicated that E-kinin was converted to E-kinin desSSRI in vivo and interacted with the receptor. Kininase II cleaves BK at the carboxy-terminal but it was ineffective for E-kinin. To detect E-kinin, monoclonal antibodies were produced in mice using 6 or 8 amino-terminal peptide of E-kinin bound to KLH as antigens. Four antibodies reacted with E-kinin but all of them cross-reacted with BK.
|
