| Co-Investigator(Kenkyū-buntansha) |
WATANABE Gen Tokyo University of Agriculture and Technology, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (90158626)
ARAI Katsuhiko Tokyo University of Agriculture and Technology, Faculty of Agriculture, Associate Professor, Institution, Department, Title of Position, 農学部, 助教授 (60175940)
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| Research Abstract |
Platelets express specific receptors such as IgE and adhesion molecules and activation mechanisms through them have been discussed. In the present research project, we investigated the possible involvement of platelets in the process of delayed-type hypersensitivity, such as contact sensitivity and atopic dermatitis. The obtained resulted are follows:
1) In vivo treatment with BA Yu3405, a (thromboxane AィイD22ィエD2) TXAィイD22ィエD2 receptor antagonist, markedly suppressed CS responses in genetically mast cell-deficient W/WィイD1vィエD1 mice and the inhibitory effect was occurred when BA Yu3405 was administered before an early initiating phase, suggesting that TXAィイD22ィエD2 may be a potent initiator of platelet-mediated CS responses.
2) When platelets were pretreated with BA Yu3405 in vitro, platelet aggregation as well as serotonin release, which is able to induce the early phase response allowing local recruitment of CS effector T cells due to direct activation of vascular endothelial cells, was inhibited.
3) Furthermore, the addition of U46619, a TXAィイD22ィエD2 agonist, or mixture of platelets and thrombin enhanced expression of both ICAM-1 and VCAM-1 on isolated mouse aortic endothelial cells, which was completely abolished by the pretreatment with BA Yu3405. These findings suggest that TXAィイD22ィエD2 generated from platelets activated with Ag may mediate initiation of CS responses through leading serotonin release from platelets and the subsequent aggregation and upregulating expression of ICAM-1 and VCAM-1 on the vascular endothelial cells.
4) Lysophosphatidylserine expressed on the membrane of the activated platelets was able to mediate nerve growth factor-dependent release of serotonin form rat peritoneal mast cells. This lysophosphatidylserine-mediated mast cell activation was demonstrated in vivo, providing novel evidence of an inflammatory cascade in allergic responses.
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