Increase of thromboplastin activity in bone marrow cells by synthetic lipid A analogs.
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概要
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Endotoxin caused cytotoxic damages of mouse bone marrow cells and an increase in thromboplastin (Tp) activity of membrane fragments of the cells. Activities of synthetic lipid A analogs were compared with those of natural lipid A. Injection of 50μg of 406 increased cytotoxicity of the cells from 16.1±0.7 (control) to 26.4±1.7%, and the activity was comparable to that of natural lipid A (27.4±1.2%, dye exclusion test). Compounds 404 and 405 also induced cytotoxicity, however, compound 403 had no activity, compounds 503 to 506, which have double acyl groups at C2′ and C3′ positions, increased cytotoxicity. Among these analogs, compound 506 had the highest activity (from control, 16.1±1.9 to 32.6±1.6%). Compound 406 or 506 caused dose-dependent induction of Tp activity in the cells. Tp activity in the cells increased by injection of as little as 6μg of compound 406, 506 or by natural lipid A. Tp activity in the cells induced by compound 406 decreased after incubation with either Concanavalin A or Polymyxin B.These findings indicate that active principle of endotoxin, as to the induction of cytotoxicity and Tp activity in bone marrow cells, is the lipid A portion. Hydroxymyristic acid at C3′ position and two phosphate groups at Cl and C4′ positions were thought to be necessary for the induction of both activities. Present studies further supported our hypothesis that membrane perturbation due to endotoxin would result in the induction of Tp activity.
- 一般社団法人 日本血栓止血学会の論文
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