| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
|
|---|
| Research Abstract |
We examined as to whether cysteinyl leukotriens (CysLT) regulate the migrative process and functions of eosinophils. Leukotriene D4 (LTD4), a Cys LT, directly and significantly induced the transendothelial migration, superoxide anion generation, and release of specific granule-protein of eosinophils. Furthermore, these parameters were all blocked by leukotriene receptor antagonist (LTRA) or anti-beta2 integrin antibody, indicating that both CysLT-receptor and beta-2 integrin adhesion molecules are critically involved. Eosinophil superoxide anion generation provoked by LTD4 was significantly augmented by recombinant adhesion molecules both ICAM-1 and VCAM-1. Furthermore, the enhanced activation of LTD4-stimulated eosinophils by those adhesion molecules was attenuated by either anti-beta2- or anti-alpha4-integrin antibody. To evaluate whether the surface expression of CysLT1 can be modified by eosinophils activator(s), the expressions were examined using flow cytometry. However, none of activators examined modified the expression of CysLT1 on eosinophils. Finally, we examined whether LTRA directly modify the migrative response of eosinophils. Pranlukast, a LTRA, blocked the eosinophil transendothelial migration in response to LTD4. On the other hand, pranlukast did not modulate eosinophil transendothelial migration in response to C-C chemokines or PAR Therefore, the inhibitory effect of pranlukast on eosinophil transmigration is highly specific for the Cys-LT1 -dependent pathway.
|
