Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli

被引:145
作者
Chatterjee, Madhumita [1 ]
Huang, Zhangsen [1 ,2 ]
Zhang, Wei [1 ]
Jiang, Lei [2 ]
Hultenby, Kjell [3 ]
Zhu, Linjing [1 ]
Hu, Hu [2 ]
Nilsson, Gunnar P. [4 ]
Li, Nailin [1 ]
机构
[1] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Med, Clin Pharmacol Unit, SE-17176 Stockholm, Sweden
[2] Zhejiang Univ, Sch Med, Dept Pathol & Pathophysiol, Hangzhou 310003, Zhejiang, Peoples R China
[3] Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Stockholm, Sweden
[4] Karolinska Univ Hosp Solna, Karolinska Inst, Clin Immunol & Allergy Unit, SE-17176 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
PROGENITOR CELLS; FACTOR-I; INFLAMMATION; ATHEROGENESIS; ANGIOGENESIS; ENDOSTATIN; ACTIVATION; ADHESION; GRANULES; VIVO;
D O I
10.1182/blood-2010-12-327007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The present study characterized platelet secretion and surface expression of proangiogenic stromal cell-derived factor-1 alpha (SDF-1 alpha) and vascular endothelial growth factor (VEGF) and antiangiogenic PF4 and endostatin on activation. The angiogenic factors presented in randomly distributed granules in resting platelets, which were peripherized on activation. Confocal and immunogold electron microscopy demonstrated that SDF1 alpha/CXCL12 and PF4/CXCL4 mostly present in different granules. Platelet activation induced marked SDF-1 alpha and endostatin but mild PF4 or no VEGF surface expression. PAR1-activating peptide (PAR1-AP), adenosine diphosphate (via P2Y1/P2Y12), and glycoprotein VI-targeting collagen-related peptide induced massive SDF-1 alpha and VEGF but modest PF4 or no endostatin release. In contrast, PAR4-AP triggered marked PF4 and sole endostatin release but limited SDF-1 alpha or VEGF secretion. Distinct platelet release of SDF-1 alpha and endostatin involved different engagements of intracellular signaling pathways. In conclusion, different platelet stimuli evoke distinct secretion and surface expression of proangiogenic and antiangiogenic factors. PAR1, adenosine diphosphate, and glycoprotein VI stimulation favors proangiogenic, whereas PAR4 promotes antiangiogenic, factor release. (Blood. 2011; 117(14): 3907-3911)
引用
收藏
页码:3907 / 3911
页数:5
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