Project/Area Number |
01571242
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
医学一般
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Research Institution | Ehime College of Health Science |
Principal Investigator |
OKADA Mariko Ehime College of Health Science, Department of Clinical Pathology, Associate Professor, 臨床検査学科, 助教授 (60111118)
|
Co-Investigator(Kenkyū-buntansha) |
TOMINAGA Akio Ehime College of Health Science, Department of Clinical Pathology, Associate Pro, 臨床検査学科, 助教授 (90036450)
SAGAWA Terutaka Ehime College of Health Science, Department of Clinical Pathology, Assistant Pro, 臨床検査学科, 助手 (90162320)
伊藤 晃 愛媛県立医療技術短期大学, 臨床検査学科, 助手 (30203128)
|
Project Period (FY) |
1989 – 1991
|
Project Status |
Completed (Fiscal Year 1991)
|
Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥700,000 (Direct Cost: ¥700,000)
|
Keywords | Platelets / Cytotoxic effect / Hemolysis / Leukemia / Protease inhibitor / 腫瘍細胞瘍害反応 / トロンビン活性化 / 透過型電顕 / 免疫電顕 / GMPー140 / 血小板依存性細胞傷害反応 / 腫瘍細胞株 / 自己赤血球溶血反応 / cAMP / シクロオキシゲナ-ゼ阻害剤 / 電子顕微鏡観察 / 活性化血小板 / 赤血球形態変化 / ガン細胞傷害反応 / エステラ-ゼ |
Research Abstract |
1) Gel-filtered human platelets (PL) exerted lytic activity on autologous red blood cells (RBC) when they were co-incubated at 37゚C with PL-activating agents in the absence of plasma. Lysis of activated PL themselves did not occur during the incubation period examined. Morphological observations showed that RBC exposed to thrombin-activated PL were fragmented and/or transformed into spherocytes. When PL and RBC were prevented from coming into direct cell to cell contact by means of a membrane barrier, their cytotoxicity was reduced but not eliminated completely. The cytotoxic activity was carried by activated PL which had lost most of the contents in granules, but not by PLfree supernatants obtained after activation of PL, and the activity was energy-dependent and cAMP-regulated. These observations suggested that the cytotoxic activity was carried by some diffusible and easily inactivated factors, which were continuously produced and liberated from activated PL. These results provide the first evidence for a direct role of activated PL in mediation of RBC-damage in the absence of any plasma factors. 2) Gel-filtered PL exerted cytotoxicity against K-562 cells, a chronic myelogenic leukemia cell line, when incubated in serumfree medium for several hours at 37゚C, a condition where no killing of normal peripheral lymphocytes occurred. Some protease inhibitors inhibited the cytotoxicity of PL. Ultrastructural observations showed that PL induced cytotoxic changes in target K-562 cells, including swelling of the cell, marginal clumping of nuclear chromatin, dilation of mitochondoria, and ruprure of the cytoplasmic membrane. These results suggest that PL may be involved in host defense against neoplasia and that certain proteases are implicated in the cytotoxic effect of PL.
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