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.
Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Harald.Langer@med.uni-tuebingen.de
%0 Journal Article
%1 Langer:2012gz
%A Langer, Harald F.
%A Choi, Eun Young
%A Zhou, Hong
%A Schleicher, Rebecca
%A Chung, Kyoung-Jin
%A Tang, Zhongshu
%A Göbel, Kerstin
%A Bdeir, Khalil
%A Chatzigeorgiou, Antonios
%A Wong, Connie
%A Bhatia, Sumeena
%A Kruhlak, Michael J.
%A Rose, John W
%A Burns, James B
%A Hill, Kenneth E
%A Qu, Hongchang
%A Zhang, Yongqing
%A Lehrmann, Elin
%A Becker, Kevin G
%A Wang, Yunmei
%A Simon, Daniel I
%A Nieswandt, Bernhard
%A Lambris, John D.
%A Li, Xuri
%A Meuth, Sven G
%A Kubes, Paul
%A Chavakis, Triantafyllos
%D 2012
%K imported
%N 9
%P 1202--1210
%R 10.1161/CIRCRESAHA.111.256370
%T Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis.
%U http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=22456181&retmode=ref&cmd=prlinks
%V 110
%X 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.
@article{Langer:2012gz,
abstract = {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.},
added-at = {2017-12-08T05:18:19.000+0100},
affiliation = {Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Harald.Langer@med.uni-tuebingen.de},
author = {Langer, Harald F. and Choi, Eun Young and Zhou, Hong and Schleicher, Rebecca and Chung, Kyoung-Jin and Tang, Zhongshu and G{\"o}bel, Kerstin and Bdeir, Khalil and Chatzigeorgiou, Antonios and Wong, Connie and Bhatia, Sumeena and Kruhlak, Michael J. and Rose, John W and Burns, James B and Hill, Kenneth E and Qu, Hongchang and Zhang, Yongqing and Lehrmann, Elin and Becker, Kevin G and Wang, Yunmei and Simon, Daniel I and Nieswandt, Bernhard and Lambris, John D. and Li, Xuri and Meuth, Sven G and Kubes, Paul and Chavakis, Triantafyllos},
biburl = {https://www.bibsonomy.org/bibtex/27329b19d84b88c49a443c81840a8378c/lambris},
date-added = {2016-04-23T19:09:47GMT},
date-modified = {2017-12-08T04:17:02GMT},
doi = {10.1161/CIRCRESAHA.111.256370},
interhash = {a8be097737d891a8af3c02c9341f308e},
intrahash = {7329b19d84b88c49a443c81840a8378c},
keywords = {imported},
language = {English},
month = apr,
number = 9,
pages = {1202--1210},
pmcid = {PMC3382058},
pmid = {22456181},
rating = {0},
timestamp = {2017-12-08T05:18:19.000+0100},
title = {{Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis.}},
uri = {\url{papers3://publication/doi/10.1161/CIRCRESAHA.111.256370}},
url = {http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=22456181&retmode=ref&cmd=prlinks},
volume = 110,
year = 2012
}