Janmey P A, Lamb J A, Ezzell R M, Hvidt S, Lind S E
Division of Experimental Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Blood. 1992 Aug 15;80(4):928-36.
The muscle and cytoskeletal protein actin is released from cells as a consequence of cell death and interacts with components of the hemostatic and fibrinolytic systems, including platelets, plasmin, and fibrin. We report here that incorporation of actin filaments into fibrin clots changes their viscoelastic properties by increasing their shear modulus at low deforming stresses and by nearly eliminating their tendency to become more rigid with increasing deformation (ie, exhibit strain-hardening). The viscoelastic effects depended on the length of the actin filaments as shown by the effects of the plasma filament-severing protein, gelsolin. Binding of actin to fibrin clots also varied with actin filament length. The plasma actin-binding proteins gelsolin and vitamin D-binding protein reduced, but did not eliminate, the incorporation of actin in the clot. Fluorescence microscopy showed a direct association of rhodamine-labeled actin filaments with the fibrin network. Incubation of clots containing long actin filaments in solutions containing physiologic concentrations of gelsolin (2 mumol/L) released 60% of the actin trapped in the clot. Reduction of the actin content of a fibrin clot by incubation in a gelsolin-containing solution resulted in an increased rate of clot lysis. The ability of plasma gelsolin to shorten actin filaments may therefore be of physiologic and potentially of therapeutic importance insofar as gelsolin-mediated diffusion of actin from the clot may restore the clot's rheologic properties and render it more sensitive to the lytic action of plasmin.
肌肉和细胞骨架蛋白肌动蛋白会因细胞死亡而从细胞中释放出来，并与止血和纤维蛋白溶解系统的成分相互作用，包括血小板、纤溶酶和纤维蛋白。我们在此报告，肌动蛋白丝掺入纤维蛋白凝块会改变其粘弹性特性，在低变形应力下增加其剪切模量，并几乎消除其随着变形增加而变得更硬的趋势（即表现出应变硬化）。如血浆丝切割蛋白凝溶胶蛋白的作用所示，粘弹性效应取决于肌动蛋白丝的长度。肌动蛋白与纤维蛋白凝块的结合也随肌动蛋白丝长度而变化。血浆肌动蛋白结合蛋白凝溶胶蛋白和维生素D结合蛋白减少了但并未消除肌动蛋白在凝块中的掺入。荧光显微镜显示罗丹明标记的肌动蛋白丝与纤维蛋白网络直接相关。在含有生理浓度凝溶胶蛋白（2 μmol/L）的溶液中孵育含有长肌动蛋白丝的凝块，会释放出被困在凝块中的60%的肌动蛋白。在含凝溶胶蛋白的溶液中孵育以降低纤维蛋白凝块的肌动蛋白含量，会导致凝块溶解速率增加。因此，血浆凝溶胶蛋白缩短肌动蛋白丝长的能力可能具有生理重要性，并且可能具有治疗重要性，因为凝溶胶蛋白介导的肌动蛋白从凝块中的扩散可能恢复凝块的流变学特性，并使其对纤溶酶的溶解作用更敏感。
