1993 Fiscal Year Final Research Report Summary
Immunological regulation of multiple organ failure by reperfusion injury.
| Project/Area Number |
04454184
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Hokkaido University |
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Principal Investigator |
UEDE Toshimitsu Hokkaido University, Institute of Immunological Science, Professor, 免疫科学研究所, 教授 (00160185)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Reperfusion Injury / Multiple Organ Failure / Cytokine / Adhesion Molecule / Endothelium |
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| Research Abstract |
The post-ischemic reperfusion injury of hearts was induced by re-establshment of coronary circulation into ischemic hearts. In order to analyze the pathogenesis of reperfusion injury and establish therapeutic means, we established a heterotopic transplantation model by Ono and Lindsey method. After 60 min ischemia, the reperfusion of cardiac tissue resulted in strong adhesion of neutrophils to endothelium. In addition, intersitial hemorrhage, inflammation, decrease of myocardial ATP,and myocardial degeneration occured with resulted in termination of myocardial contraction. Administration of monoclonal antibody, R2-1A6 significantly inhibited the binding of neutrophils to endothelium, subsequent inflammation and myocardial degeneration. We also established blood perfused isolated rat heart model (Langendorff model). In this model, we can analyze the functional aspect of ischemic hearts in reperfusion injury. Cytokine gene expression and left ventricular function after reperfusion were studied. Although neutrophil-mediated inflammation and myocardial degeneration was not obvious, the deterioration of ventricle function wea evident after reperfusion. In addition, IL-1alpha was specifically detected upon reperfusion of ischemic hearts, indicating that cytokines such as IL-1alpha may be directly involved in pathogenesis of reperfusion injury.
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Research Products
(15 results)
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[Publications] Nomura, N., Uno, E., Tamura, Y., Suzuki, A., Kikuchi, K.and Uede, T.: "Vascular endothelial cells capable of binding lymphocytes express R2-1A6 antigen." Allergy and Immunology (Life Sci Adv). 10. 33-39 (1991)
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[Publications] Nomura, N., Uno, E., Tamatani, T., Miyasaka, M., Suzuki, A., Kikuchi, K.and Uede, T.: "Functional analysis of mononuclear cells infiltrating into tumors. VI.The effect of lymphocyte chemotactic factors on lymphocyte adhesion to endothelial cells." Int.Immunol. 4. 407-415 (1992)
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[Publications] Kawaguchi, S., Kikuchi, K., Ishii, S., Takada, Y., Kobayashi, S.and Uede, T.: "VLA-4 molecules on tumor cells initiate an adhesive interaction with VCAM-1 molecules on endothelial cell surface." Jpn.J.Cancer Res.83. 1304-1316 (1992)
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