Okada M, Kodama T, Tominaga A, Kon K, Sagawa T, Utsumi S
Department of Clinical Pathology, Ehime College of Health Science, Japan.
Br J Haematol. 1992 Sep;82(1):142-50. doi: 10.1111/j.1365-2141.1992.tb04606.x.
Gel-filtered human platelets exerted lytic activity on autologous red blood cells (RBC) when they were coincubated at 37 degrees C with platelet-activating agents, such as thrombin, collagen, ADP, LPS or PMA in the absence of plasma. Lysis of activated platelets themselves did not occur during the incubation period examined. Morphological observations showed that RBC exposed to thrombin-activated platelets were fragmented and/or transformed into spherocytes. This haemolytic reaction by thrombin-activated platelets did not occur at 4 degrees C, or in the presence of agents which inhibited glycolysis or elevated intracellular levels of cAMP, indicating that energy-dependent and cAMP-regulated platelet metabolism was required for this reaction. When platelets and RBC were incubated in the same vessel, but were prevented from coming into direct cell to cell contact by means of a membrane barrier, their cytotoxicity was reduced but not eliminated completely. No cytotoxic activity against RBC was detected in platelet-free supernatants obtained by centrifugation after activation of platelets with thrombin. On the contrary, activated and washed platelets retained the activity. These observations suggested that the cytotoxic activity was carried by some diffusible and easily inactivated factors, which were continuously produced and liberated from activated platelets. Cyclo-oxygenase inhibitors inhibited the haemolytic activity of thrombin-activated platelets, suggesting a role for some products of platelet-cyclo-oxygenase pathway in platelet-mediated haemolysis. These results provide the first evidence for a direct role of activated platelets in mediation of RBC-damage in the absence of any plasma factors.
当凝胶过滤的人血小板在37℃下与血小板激活剂(如凝血酶、胶原蛋白、ADP、LPS或PMA)在无血浆的情况下共同孵育时,它们对自体红细胞(RBC)具有溶解活性。在所检测的孵育期间,活化血小板本身未发生溶解。形态学观察表明,暴露于凝血酶激活血小板的红细胞发生了碎片化和/或转化为球形红细胞。凝血酶激活血小板引起的这种溶血反应在4℃时不发生,或在存在抑制糖酵解或提高细胞内cAMP水平的试剂时也不发生,这表明该反应需要能量依赖和cAMP调节的血小板代谢。当血小板和红细胞在同一容器中孵育,但通过膜屏障阻止它们直接细胞间接触时,它们的细胞毒性降低但未完全消除。在用凝血酶激活血小板后通过离心获得的无血小板上清液中未检测到对红细胞的细胞毒性活性。相反,活化并洗涤过的血小板保留了活性。这些观察结果表明,细胞毒性活性是由一些可扩散且易失活的因子携带的,这些因子由活化血小板持续产生并释放。环氧化酶抑制剂抑制凝血酶激活血小板的溶血活性,提示血小板环氧化酶途径的某些产物在血小板介导的溶血中起作用。这些结果首次证明了在没有任何血浆因子的情况下,活化血小板在介导红细胞损伤中起直接作用。