The role of adrenomedullin in immunesystem in sepsis

Research Project

Project/Area Number	11671523
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Anesthesiology/Resuscitation studies
Research Institution	Hyogo College of Medicine (2000) Teikyo University (1999)
Principal Investigator	ONO Yukari Hyogo College of Medicine. Research Associate, 医学部, 助手 (30312002)
Co-Investigator(Kenkyū-buntansha)	OKADA Kazuo Teikyo Univ. School of Medicine. professor, 医学部, 教授 (30082093) TASHIRO Chikara Hyogo College of Medicine. professor, 医学部, 教授 (20107048) KANGAWA Kenji National Cardiovascular Center., 研究所, 部長 (00112417) 中村到帝京大学, 医学部, 助手 (50307196)
Project Period (FY)	1999 – 2000
Project Status	Completed (Fiscal Year 2000)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,900,000) Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000) Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
Keywords	adrenomedullin / sepsis / lipopolysaccharide / thymus / receptor / エンドトキシン / CRLR / RAMPs / 肺
Research Abstract	Plasma concentrations of adrenomedullin (AM) are markedly increased during sepsis, but the role of AM has not been clarified. Coexpression of calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP) 2 or 3 have been reported to form the adrenomedullin (AM) specific receptor. We examined the expression of CRLR and RAMP1, 2, and 3 in several tissues from mice in a sepsis model induced by lipopolysaccharide (LPS). High expression of CRLR and RAMP2 mRNA was observed in lungs of normal mice, but it was markedly decreased in endotoxemic mice. It is suggested that the abundant binding sites of AM in lungs are formed by CRLR and RAMP2 in healthy subjects and that their reduction should contribute to the increase of plasma AM concentrations during sepsis. In contrast, LPS treatment markedly increased RAMP3 gene expression in lungs, spleen, and thymus. It is revealed that the distributions of receptor or binding sites of AM are changed in sepsis, and it is suggested that AM plays distinct roles in the clinical course of this syndrome.