2004 Fiscal Year Final Research Report Summary
Relative contribution of various adhesion molecules to tissue injury induced by immune complex deposition
| Project/Area Number |
15591171
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kanazawa University |
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Principal Investigator |
SATO Shinichi Kanazawa Univ., Grad.Sch.of Medical Science Dermatology, Associate Professor, 大学院・医学系研究科, 助教授 (20215792)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEHARA Kazuhiko Kanazawa Univ., Grad.Sch.of Medical Science Dermatology, Professor, 大学院・医学系研究科, 教授 (50142253)
HASEGAWA Minoru Kanazawa Univ., Grad.Sch.of Medical Science Dermatology, Assistant Professor, 医学部附属病院, 講師 (50283130)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Immune complex / P-selectin / E-selectin / Cell adhesion molecule / vasculitis / Arthus reaction / ICAM-1 / L-selectin |
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| Research Abstract |
Immune complex-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the relative contribution of adhesion molecules, including selectins and ICAM-1, in this pathogenetic process, the cutaneous passive Arthus reaction was examined in mice lacking E-selectin, P-selectin, or both L-selectin and ICAM-1 with anti-P-or E-selectin mAbs. Edema and hemorrhage were significantly reduced in P-selectin^<-/-> mice compared with wild type mice while they were not inhibited in E-selectin^<-/-> mice. Combined E and P-selectin blockade resulted in more significant reduction relative to L-selectin/ICAM-1^<-/-> as well as P-selectin^<-/-> mice. Remarkably, both E-and P-selectin blockade in L-selectin/ICAM-1^<-/-> mice completely abrogated edema and hemorrhage. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells that expressed significant levels of P-selectin glycoprotein ligand-1. Similarly reduced infiltration of neutrophils and mast cells was observed in the peritoneal Arthus reaction and was associated partly with the decreased production of tumor necrosis factor-□ and interleukin-6. The results of this study indicate that both endothelial selectins contribute predominantly to the Arthus reaction by regulating mast cell and neutrophil infiltration and that the full development of the Arthus reaction is mediated cooperatively by all selectins and ICAM-1.
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