Cho Moon J, Pestina Tamara I, Steward Shirley A, Jackson Carl W, Kent Gartner T
Department of Microbiology and Molecular Cell Sciences, University of Memphis, Memphis, Tennessee 38152, USA.
Biochem Biophys Res Commun. 2002 Apr 12;292(4):916-21. doi: 10.1006/bbrc.2002.6738.
The work presented here demonstrates that platelets from mice lacking LAT (linker for the activation of T cells) show reversible aggregation in response to concentrations of collagen that cause TxA2/ADP-dependent irreversible aggregation of control platelets. The aggregation defect of the LAT-deficient platelets was shown to be the result of almost no TxA2 production and significantly diminished ADP secretion. In contrast, the LAT deficiency does not affect aggregation induced by high concentrations of collagen because that aggregation is not dependent on TxA2 and/or ADP. Even though ADP and TxA2 provide amplification signals for platelet activation in response to low concentrations of collagen, LAT-deficient platelets hyperaggregate to low levels of U46619, a TxA2 analog, or ADP. Though the mechanism(s) of costimulatory signals by collagen, ADP, and TxA2 remains unidentified, it is clear that LAT plays a positive role in collagen-induced, TxA2/ADP-dependent aggregation, and a negative role in TxA2 or ADP-induced platelet aggregation.
此处展示的研究工作表明，缺乏LAT（T细胞活化连接蛋白）的小鼠血小板，在受到能使对照血小板发生TxA2/ADP依赖性不可逆聚集的胶原浓度刺激时，会出现可逆性聚集。结果显示，LAT缺陷型血小板的聚集缺陷是由于几乎不产生TxA2且ADP分泌显著减少所致。相比之下，LAT缺陷并不影响高浓度胶原诱导的聚集，因为该聚集不依赖于TxA2和/或ADP。尽管ADP和TxA2为低浓度胶原刺激下的血小板活化提供放大信号，但LAT缺陷型血小板会对低水平的TxA2类似物U46619或ADP发生过度聚集。虽然胶原、ADP和TxA2的共刺激信号机制尚不明晰，但很明显，LAT在胶原诱导的、TxA2/ADP依赖性聚集中起积极作用，而在TxA2或ADP诱导的血小板聚集中起消极作用。
