The actin cytoskeleton differentially regulates platelet α-granule and dense-granule secretion

被引:106
作者
Flaumenhaft, R
Dilks, JR
Rozenvayn, N
Monahan-Earley, RA
Feng, D
Dvorak, AM
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Hemostasis Thrombosis & Vasc Biol Res,Dept Me, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA
关键词
D O I
10.1182/blood-2004-04-1392
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Stimulation of platelets with strong agonists results in centralization of cytoplasmic organelles and secretion of granules. These observations have led to the supposition that cytoskeletal contraction facilitates granule release by promoting the interaction of granules with one another and with membranes of the open canalicular system. Yet, the influence of the actin cytoskeleton in controlling the membrane fusion events that mediate granule secretion remains largely unknown. To evaluate the role of the actin cytoskeleton in platelet granule secretion, we have assessed the effects of latrunculin A and cytochalasin E on granule secretion. Exposure of platelets to low concentrations of these reagents resulted in acceleration and augmentation of agonist-induced a-granule secretion with comparatively modest effects on dense granule secretion. In contrast, exposure of platelets to high concentrations of latrunculin A inhibited agonist-induced alpha-granule secretion but stimulated dense granule secretion. Incubation of permeabilized platelets with low concentrations of latrunculin A primed platelets for Ca2+- or guanosine triphosphate (GTP)-gamma-S-induced alpha-granule secretion. Latrunculin A-dependent alpha-granule secretion was inhibited by antibodies directed at vesicle-associated membrane protein (VAMP), demonstrating that latrunculin A supports soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein-dependent membrane fusion. These results indicate that the actin cytoskeleton interferes with platelet exocytosis and differentially regulates alpha-granule and dense granule secretion.
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页码:3879 / 3887
页数:9
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