| Co-Investigator(Kenkyū-buntansha) |
MADOIWA Seiji Jichi Medical School, Cell and molecular medicine, Instructor, 医学部, 講師 (70296119)
MIMURO Jun Jichi Medical School, Cell and molecular medicine, Instructor, 医学部, 講師 (10221607)
|
|---|
| Research Abstract |
We have hypothesized that there might be a kind of cross-talk between plasminogen activator-plasmin dependent fibrinolytic system and granulocyte-derived elastase dependent one, according to the following observations : 1, congenital plasminogen-deficient patients have no intravascular thrombophilic episodes. The granulocyte-derived elastase level of these patients in plasma is 10-100 times higher than that of the normal. Moreover, infusion of purified plasminogen decreases the level to a normal range. 2, plasminogen activator-plasmin dependent fibrinolytic system is supposed to be shutdown by remarkable increase of plasminogen activator inhibitor-1 in patient with disseminated intravascular coagulation associated with severe sepsis. Using ELISA system employing a monoclonal antibody specific to the granulocyte-derived elastase-fragment D species of human fibrin, we found that the elastase fibrin-digests were mostly elevated in these patients.
To support this hypothesis, we used plasminogen-deficient mice (KO mice) with synthetic elastase inhibitor. After the age of 7 weeks, 19% of KO mice develop rectal prolapse due to intravascular thrombosis in microcirculation. Unexpectedly, administration of elastase inhibitor protected KO mice from rectal prolapse. In addition, the amount of leukocyte infiltration and a fibrin deposit in the lung after lipopolysacharride loading were also decreased by concomitant elastase inhibition. These results suggest a cross-talk between two systems is more complicated and much more needs to be learned about the role of elastase in relation to alternative fibrinolytic system.
|
