期刊
CIRCULATION RESEARCH
卷 110, 期 9, 页码 1202-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.111.256370
关键词
platelets; experimental autoimmune encephalomyelitis; vascular inflammation; autoimmune disease
资金
- National Institutes of Health [HL57506, HL085816, HL073852]
- National Cancer Institute
- National Institute on Aging
- National Multiple Sclerosis Society [RG3411B4/1]
- German Research Foundation
- Novartis Foundation for Therapeutic Research
- IZKF of the University of Tubingen [1868-0-0]
- Tuebingen Platelet Investigative Consortium (TuePIC)
- Clinical Research Unit (KFO) [274]
- Volkswagen Foundation
Rationale: Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function of platelets in inflammatory and autoimmune pathologies is thus far poorly defined. Objective: We addressed the role of platelets in mediating CNS inflammation in EAE. Methods and Results: We found that platelets were present in human MS lesions as well as in the CNS of mice subjected to EAE but not in the CNS from control nondiseased mice. Platelet depletion at the effector-inflammatory phase of EAE in mice resulted in significantly ameliorated disease development and progression. EAE suppression on platelet depletion was associated with reduced recruitment of leukocytes to the inflamed CNS, as assessed by intravital microscopy, and with a blunted inflammatory response. The platelet-specific receptor glycoprotein Ib alpha (GPIb alpha) promotes both platelet adhesion and inflammatory actions of platelets and targeting of GPIb alpha attenuated EAE in mice. Moreover, targeting another platelet adhesion receptor, glycoprotein IIb/IIIa (GPIIb/IIIa), also reduced EAE severity in mice. Conclusions: Platelets contribute to the pathogenesis of EAE by promoting CNS inflammation. Targeting platelets may therefore represent an important new therapeutic approach for MS treatment. (Circ Res. 2012;110:1202-1210.)
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