| Co-Investigator(Kenkyū-buntansha) |
NAKAZAWA Ayami SHINSHU UNIVERSITY, SCHOOL OF MEDICINE, RESEARCH FELLOW, 医学部, 助手 (90273078)
JOHKURA Kouhei SHINSHU UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (30303473)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
The failure of bio-defence of the peritoneal and pleural cavity, which is closely associated with cellular adhesion molecules, causes fatal damage to the body such as sepsis, but even if healing, severe adhesion of the serous membranes occurs inevitably and leads to intestinal obstruction or inhibition of the respiratory movement. In this project, the mechanism of the bio-defence and inhibition of adhesion in both cavities are analyzed with cell biological methods and discussed.
1. Mechanism of the bio-defence of the peritoneal and pleural cavities. Interactions between ICAM-1 and LFA-1 & Mac-1 in normal, between VCAM-1 and VLA-4 in addition to ICAM-1 and LFA-1 in moderate inflammation and between fibronectin and VLA-4 in addition to VCAM-1 and VLA-4 in severe inflammation work according to each inflammatory stage. The first interaction between ICAM-1 and LFA-1 & Mac-1 promotes light adhesion, is done by microvilli of the mesothelial cells and microvilli or ruffles of leukocytes and pro
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bably used for migration. The second interaction between VCAM-1 and VLA-4 is necessary for fixation of leukocytes, which causes local secretion of cytokines. The last interaction brings about pathological adhesion through fibrous networks due to fibronectin.
2. Source of leukocytes. In the peritoneal cavity, milky spots are well known as the supplying site for leukocytes. The area is always activated. Expression of ICAM-1 is four times higher than other areas. Leukocytes proliferate at that region. In the pleural cavity, the connective tissue near the costae including vascular network and adipocytes is identical to milky spots. The mesothelial cells at that region proliferate markedly, which suggest they are stem cells.
3. Inhibition of migration and adhesion. In the peritoneal cavity, ICAM-1, VCAM-1, VLA-4, LFA-1,Mac-1 are blocked with antibodies, which cause drastic inhibition of leukocyte migration. From this result and previous observations, inhibition of VCAM-1 and VLA-4 may be proposed to suppress adhesion of serous membranes. Less
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