INTEGRIN ALPHA-2-BETA-1-INDEPENDENT ACTIVATION OF PLATELETS BY SIMPLE COLLAGEN-LIKE PEPTIDES - COLLAGEN TERTIARY (TRIPLE-HELICAL) AND QUATERNARY (POLYMERIC) STRUCTURES ARE SUFFICIENT ALONE FOR ALPHA-2-BETA-1-INDEPENDENT PLATELET REACTIVITY
INTEGRIN ALPHA-2-BETA-1-INDEPENDENT ACTIVATION OF PLATELETS BY SIMPLE COLLAGEN-LIKE PEPTIDES - COLLAGEN TERTIARY (TRIPLE-HELICAL) AND QUATERNARY (POLYMERIC) STRUCTURES ARE SUFFICIENT ALONE FOR ALPHA-2-BETA-1-INDEPENDENT PLATELET REACTIVITY
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DOI：
10.1042/bj3060337
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发表时间：
1995-03-01
影响因子：
4.1
通讯作者：
BARNES, MJ
中科院分区：
文献类型：
--
作者：
MORTON, LF;HARGREAVES, PG;BARNES, MJ
本文研究了两种简单的类胶原合成肽Gly-Lys-Hyp-（Gly-Pro-Hyp）（10）-Gly-Lys-Hyp-Gly和Gly-Cys-Hyp-（Gly-Pro-Hyp）（10）-Gly-Cys-Hyp-Gly的血小板反应性。两种肽在溶液中均呈稳定的三螺旋构象。交联后，这两种肽被证明是高度血小板聚集性的，比胶原纤维更活跃，在低至20 ng/ml的浓度下诱导聚集。这些肽在溶液中形成微聚集体，交联被认为可以稳定这些结构，使其在37 ℃下表达血小板反应性。与胶原纤维一样，这些肽引起血小板分泌和花生四烯酸盐从血小板膜脂质中释放，以及整联蛋白α IIb β 3的活化，最终导致聚集。针对整合素α 2 β 1的单克隆抗体未能阻止聚集、花生四烯酸释放或血小板粘附至肽。我们的研究结果表明，胶原蛋白可以激活血小板的机制是独立的整合素α 2 β 1和胶原蛋白的三级和四级结构是足够的活动，而不涉及高度特异性的细胞识别序列。
The platelet reactivities of two simple collagen-like synthetic peptides, Gly-Lys-Hyp-(Gly-Pro-Hyp)(10)-Gly-Lys-Hyp-Gly and Gly-Cys-Hyp-(Gly-Pro-Hyp)(10)-Gly-Cys-Hyp-Gly, were investigated. Both peptides adopted a stable triple-helical conformation in solution. Following cross-linking, both peptides proved to be highly platelet-aggregatory, more active than collagen fibres, inducing aggregation at concentrations as low as 20 ng/ml. These peptides formed microaggregates in solution, and crosslinking was thought to stabilize these structures, allowing expression of their platelet reactivity at 37 degrees C. Like collagen fibres, the peptides caused platelet secretion and release of arachidonate from platelet membrane lipids as well as activation of integrin alpha IIb beta 3 culminating in aggregation. Monoclonal antibodies directed against the integrin alpha 2 beta 1 failed to prevent aggregation, release of arachidonate or platelet adhesion to the peptides. Our results indicate that collagen can activate platelets by a mechanism that is independent of integrin alpha 2 beta 1 and for which collagen tertiary and quaternary structures are sufficient alone for activity without the involvement of highly specific cell-recognition sequences.