Unique Endotoxin-Neutralizing Proteins:Inhibition of Endotoxin-Induced Tissue Factor Generation
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概要
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Cationic antibacterial proteins (CAP), intracellular LPS-binding proteins, were prepared from rabbit peritoneal granulocytes using an assay the agglutination of erythrocytes coated with Re-LPS. Molecular weight of CAP estimated by SDS-PAGE was 7kDa (CAP-7) and 18kDa (CAP-18), and CAP-7 had high contents of cationic residues. LPS activates murine macrophages and human blood monocytes to generate tissue factor (tissue thromboplastin). After 18 hours incubation of LPS preparations with CAP (heparin-sepharose fraction), S-LPS, Re-LPS and lipid A-induced tissue factor activities were inhibited. S-LPS was inactivated more rapidly than Re-LPS and lipid A. Within 1 hour incubation, purified CAP-18 inhibited about 75% of the activity of S-LPS. CAP-7 also inhihited LPS-induced tissue factor generation by human blood monocytes. LPS-binding, and LPS-neutralizing activates of CAP-7 were highter than those of CAP-18. Synthetic peptied #197-1 (indentical structure to CAP-7) also showed LPS-binding and LPS-neutralizing activities.DIC manifestation in endotoxemia, due to gram-negative bacterial infections, are controlled by CAP released from granulocytes. In addition, CAP-7 and CAP-18 may have therapeutic potential for septic and endotoxin shock.
- 一般社団法人 日本血栓止血学会の論文
一般社団法人 日本血栓止血学会 | 論文
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