title: Platelets recognize brain-specific glycolipid structures, respond to neurovascular damage and promote neuroinflammation.
abstract: Platelets respond to vascular damage and contribute to inflammation, but their role in the neurodegenerative diseases is unknown. We found that the systemic administration of brain lipid rafts induced a massive platelet activation and degranulation resulting in a life-threatening anaphylactic-like response in mice. Platelets were engaged by the sialated glycosphingolipids (gangliosides) integrated in the rigid structures of astroglial and neuronal lipid rafts. The brain-abundant gangliosides GT1b and GQ1b were specifically recognized by the platelets and this recognition involved multiple receptors with P-selectin (CD62P) playing the central role. During the neuroinflammation, platelets accumulated in the central nervous system parenchyma, acquired an activated phenotype and secreted proinflammatory factors, thereby triggering immune response cascades. This study determines a new role of platelets which directly recognize a neuronal damage and communicate with the cells of the immune system in the pathogenesis of neurodegenerative diseases.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ilya
authors.initials: I
authors.lastname: Sotnikov
authors.forename: Tatyana
authors.initials: T
authors.lastname: Veremeyko
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Starossom
authors.forename: Natalia
authors.initials: N
authors.lastname: Barteneva
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Ponomarev
mesh_terms: D000707:Anaphylaxis / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D001692:Biological Transport; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D015550:Cell Degranulation; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D005732:Gangliosides / Q000276:immunology; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D005732:Gangliosides; D006017:Glycolipids; D011956:Receptors, Cell Surface
references.citation: Lab Invest. 2007 Sep;87(9):851-7
references.pmid: 17632542
references.citation: Methods. 1998 Nov;16(3):282-92
references.pmid: 10071067
references.citation: J Neurosci Res. 2008 Sep;86(12):2624-40
references.pmid: 18500752
references.citation: Ann N Y Acad Sci. 2010 Oct;1207:11-7
references.pmid: 20955420
references.citation: Nat Chem Biol. 2005 Jul;1(2):93-7
references.pmid: 16408005
references.citation: Circ Res. 2012 Apr 27;110(9):1202-10
references.pmid: 22456181
references.citation: Cancer Res. 1988 Jul 1;48(13):3728-32
references.pmid: 3288333
references.citation: J Comp Neurol. 2001 Jan 29;430(1):131-44
references.pmid: 11135250
references.citation: Cell Mol Neurobiol. 2005 Feb;25(1):5-23
references.pmid: 15962506
references.citation: Science. 2010 Jan 29;327(5965):580-3
references.pmid: 20110505
references.citation: Biochim Biophys Acta. 2007 Aug;1768(8):1943-51
references.pmid: 17321494
references.citation: J Pharmacol Exp Ther. 1991 Sep;258(3):830-6
references.pmid: 1653841
references.citation: Biochim Biophys Acta. 2010 Aug;1801(8):860-7
references.pmid: 20303415
references.citation: Curr Opin Struct Biol. 2009 Oct;19(5):549-57
references.pmid: 19608407
references.citation: Annu Rev Neurosci. 2007;30:235-58
references.pmid: 17506642
references.citation: Cardiovasc Hematol Disord Drug Targets. 2008 Jun;8(2):99-117
references.pmid: 18537597
references.citation: Thromb Res. 2000 Sep 1;99(5):495-502
references.pmid: 10973680
references.citation: Mult Scler. 2003 Dec;9(6):540-9
references.pmid: 14664465
references.citation: J Biol Chem. 2003 Nov 28;278(48):48245-50
references.pmid: 14500706
references.citation: J Thromb Haemost. 2003 Sep;1(9):1897-905
references.pmid: 12941029
references.citation: Nat Protoc. 2007;2(6):1490-8
references.pmid: 17545985
references.citation: Mol Neurobiol. 2010 Jun;41(2-3):172-9
references.pmid: 20157789
references.citation: Infect Immun. 1987 Apr;55(4):1004-8
references.pmid: 3557617
references.citation: J Biol Chem. 2002 Nov 22;277(47):45299-305
references.pmid: 12235144
references.citation: Thromb Res. 2002 Apr 15;106(2):137-41
references.pmid: 12182913
references.citation: Nat Med. 2011 Jan;17(1):64-70
references.pmid: 21131957
references.citation: Am J Physiol. 1984 Mar;246(3 Pt 2):R277-88
references.pmid: 6367490
references.citation: Int J Med Microbiol. 2011 Mar;301(3):204-12
references.pmid: 21115396
references.citation: Pharm Res. 1997 Oct;14(10):1309-15
references.pmid: 9358541
references.citation: Transplantation. 2008 Nov 15;86(9):1267-74
references.pmid: 19005409
references.citation: J Thromb Haemost. 2009 Nov;7(11):1759-66
references.pmid: 19691483
references.citation: Nat Immunol. 2011 Oct 30;12(12):1194-201
references.pmid: 22037602
references.citation: Bioorg Med Chem Lett. 2003 Feb 24;13(4):675-8
references.pmid: 12639556
references.citation: J Cell Physiol. 1991 Apr;147(1):7-16
references.pmid: 2037624
references.citation: J Lipid Res. 2009 Apr;50(4):759-67
references.pmid: 19060326
references.citation: Nat Med. 2008 Jun;14(6):648-55
references.pmid: 18488037
references.citation: Biochim Biophys Acta. 2009 Jan;1788(1):184-93
references.pmid: 18835549
references.citation: Neurobiol Aging. 2007 Mar;28(3):336-42
references.pmid: 16442186
references.citation: Blood. 2008 Nov 1;112(9):3555-62
references.pmid: 18676880
references.citation: Trends Immunol. 2005 Jun;26(6):289-91
references.pmid: 15922942
references.citation: Neurobiol Aging. 2010 Sep;31(9):1503-15
references.pmid: 18950899
references.citation: Br J Pharmacol. 2002 Sep;137(2):146-52
references.pmid: 12208770
references.citation: Oral Microbiol Immunol. 2004 Feb;19(1):26-30
references.pmid: 14678471
references.citation: Nat Genet. 2004 Nov;36(11):1147-8
references.pmid: 15514666
references.citation: Int Arch Allergy Immunol. 1998 Jul;116(3):188-95
references.pmid: 9693266
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):360-5
references.pmid: 14691248
references.citation: Neurochem Res. 2007 Feb;32(2):213-28
references.pmid: 17031566
references.citation: Arch Neurol. 1998 Apr;55(4):530-6
references.pmid: 9561982
references.citation: Blood. 2010 Apr 29;115(17):3427-36
references.pmid: 20194899
references.citation: J Cell Sci. 2004 Aug 15;117(Pt 18):4067-76
references.pmid: 15292398
references.citation: Neurochem Res. 1990 May;15(5):519-22
references.pmid: 2370944
references.citation: Glycoconj J. 2004;20(1):33-8
references.pmid: 14973368
references.citation: Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12147-52
references.pmid: 9770454
references.citation: J Neurosci Res. 1986;15(3):303-21
references.pmid: 3701884
references.citation: J Clin Invest. 1998 Feb 1;101(3):667-76
references.pmid: 9449701
references.citation: J Neuroimmunol. 2010 Dec 15;229(1-2):180-91
references.pmid: 20832870
references.citation: J Thromb Haemost. 2007 Apr;5(4):661-9
references.pmid: 17403200
references.citation: J Supramol Struct. 1978;8(1):1-17
references.pmid: 366282
references.citation: Acta Neurol Scand. 1987 Aug;76(2):79-85
references.pmid: 2960124
references.citation: Curr Opin Hematol. 2009 May;16(3):209-14
references.pmid: 19318941
references.citation: Cell Mol Life Sci. 2010 Feb;67(4):499-511
references.pmid: 20016997
references.citation: Biochim Biophys Acta. 1986 Mar 21;876(1):36-47
references.pmid: 3947668
references.citation: Biochim Biophys Acta. 2008 Mar;1780(3):421-33
references.pmid: 17991443
references.citation: Pediatr Blood Cancer. 2006 Mar;46(3):292-9
references.pmid: 16317740
references.citation: Acta Neurobiol Exp (Wars). 2011;71(1):113-28
references.pmid: 21499332
references.citation: Am J Pathol. 2000 Jul;157(1):69-74
references.pmid: 10880377
references.citation: Biochem Biophys Res Commun. 1995 Aug 4;213(1):96-103
references.pmid: 7639768
references.citation: J Neuroinflammation. 2008 Jun 27;5:27
references.pmid: 18588683
references.citation: Appl Environ Microbiol. 1999 Jan;65(1):45-52
references.pmid: 9872758
references.citation: Arch Biochem Biophys. 2000 Apr 15;376(2):371-6
references.pmid: 10775425
references.citation: Cell Mol Life Sci. 2006 Jun;63(12):1331-54
references.pmid: 16596337
references.citation: Arch Gerontol Geriatr. 1985 Jul;4(2):125-32
references.pmid: 4037931
references.citation: Biochim Biophys Acta. 1988 Feb 22;968(2):167-71
references.pmid: 3342263
references.citation: Lancet. 1965 Nov 27;2(7422):1109-10
references.pmid: 4158810
references.citation: Science. 2007 Sep 21;317(5845):1767-70
references.pmid: 17885137
references.citation: Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):519-24
references.pmid: 10073952
references.citation: Thromb Res. 2010 Apr;125(4):292-6
references.pmid: 20004006
references.citation: J Neuroimmunol. 2006 Aug;177(1-2):209-14
references.pmid: 16806499
references.citation: J Neuroinflammation. 2010 Feb 03;7:10
references.pmid: 20128908
references.citation: Methods Enzymol. 2003;373:3-16
references.pmid: 14714393
references.citation: Neuron. 2000 Oct;28(1):41-51
references.pmid: 11086982
references.citation: Am Heart J. 2010 Oct;160(4):595-604
references.pmid: 20934552
references.citation: Circulation. 1993 Nov;88(5 Pt 1):2035-44
references.pmid: 8222096
references.citation: Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2362-7
references.pmid: 21071699
references.citation: Brain Res. 1984 Dec 24;324(2):379-83
references.pmid: 6397235