| Co-Investigator(Kenkyū-buntansha) |
EGAWA Hiroto Kyoto University, Kyoto university hospital, Associate professor, 医学研究科, 助教授 (40293865)
MATSUMOTO Shinichi Fujita Health University, Faculty of Medicine, Professor, 医学部, 教授 (70359834)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
We hypothesized that the S100A8/A9 complex is effective in the suppression of acute inflammatory changes. To clarify such functional role of the S100A8/A9 complex in acute inflammatory disorder, the complex purified from human leukocytes (approx. 1 mg) was intraperitoneally injected into rats 1.0 h or 3.5 h after an injection of lipopolysaccharide (LPS). The serum levels of interleukin-6 (IL-6) and nitric oxide (NOx) were significantly decreased in the treated rats. Conversely, when anti-S100A8/A9 complex IgG was injected into the tail blood vessel of a rat 1.0 h after the injection of LPS, the serum concentration of IL-6 increased slightly, indicating that the antibody immunoregulatorily blocked the activity of the complex as an anti-inflammatory protein in vivo. In addition, the S100A8/A9 complex bound non-specifically with interleukin-1b (IL-1β), IL-6 and TNF-α in vitro, suggesting that the complex could bind with these cytokines in vivo. A large number of endogenous S100A8/A9 compl
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ex-positive cells that accumulated in the inflamed region in the liver 6 h after the injection of LPS were microscopically observed, while apparent inflammatory changes were not found microscopically in other organs, such as the kidney, lung and spleen. In rats treated with the S100A8/A9 complex, neither acute inflammatory changes nor S100A8/A9 complex-positive cells were also observed microscopically in the liver tissue. These findings suggest that the S100A8/A9 complex indirectly suppresses the overproduction of NOx from activated neutrophils and/or macrophages by neutralizing the activity of pro-inflammatory cytokines. Thus, the S100A8/A9 complex may play an important role in the suppression of acute inflammation by modulating the vital activity of pro-inflammatory cytokines in vivo.
On the other hand, we investigated a patient with type-I diabetes mellitus undergoing pancreatic islets transplantation. In this patient, we evaluated clinical usefulness of the serial measurement of serum S 100A8/A9 complex levels for detecting acute inflammatory responses associated with rejection of transplanted pancreatic islets. The serum S100A8/A9 complex was a more sensitive marker for acute inflammation associated with islets transplant rejection than the serum CRP. Thus, the serial measurement of the serum S100A8/A9 complex concentration is useful for monitoring the patients with pancreatic islets transplantation. Less
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