Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain barrier disruption: Implications for the pathogenesis of multiple sclerosis

Neuropathology and Applied Neurobiology

Volumn 39, Issue 3, 2013, Pages 270-283

  D'Aversa, T G ^a,c   Eugenin, E A ^a,d   Lopez, L ^a   Berman, J W ^a,b  

^a Departments of Pathology and Urology   (United States)

^b ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^c IONA COLLEGE   (United States)

^d PUBLIC HEALTH RESEARCH INSTITUTE   (United States)

Author keywords

Blood brain barrier; CCL2; EAE; IL 6; MBP; MS

Indexed keywords

CLAUDIN 1; GELATINASE A; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE 14; MONOCYTE CHEMOTACTIC PROTEIN 1; MYELIN BASIC PROTEIN; OCCLUDIN; TIGHT JUNCTION PROTEIN;

ARTICLE; BLOOD BRAIN BARRIER; CONTROLLED STUDY; CORRELATION ANALYSIS; ENDOTHELIUM CELL; ENZYME LINKED IMMUNOSORBENT ASSAY; FAR WESTERN BLOTTING; HUMAN; HUMAN CELL; INFLAMMATION; MULTIPLE SCLEROSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; SIGNAL TRANSDUCTION;

BLOOD-BRAIN BARRIER; BLOTTING, WESTERN; CAPILLARY PERMEABILITY; CHEMOKINE CCL2; ENDOTHELIAL CELLS; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; INTERLEUKIN-6; MULTIPLE SCLEROSIS; MYELIN BASIC PROTEIN;

EID: 84866176888     PISSN: 03051846     EISSN: 13652990     Source Type: Journal    
DOI: 10.1111/j.1365-2990.2012.01279.x     Document Type: Article

References (99)

1. Pouly S, Antel JP. Multiple sclerosis and central nervous system demyelination. J Autoimmun 1999; 13: 297-306
2. Hallpike JF, Adams CW. Proteolysis and myelin breakdown: a review of recent histochemical and biochemical studies. Histochem J 1969; 1: 559-78
3. Lutton JD, Winston R, Rodman TC. Multiple sclerosis: etiological mechanisms and future directions. Exp Biol Med (Maywood) 2004; 229: 12-20
4. Kooi EJ, van Horssen J, Witte ME, Amor S, Bo L, Dijkstra CD, van der Valk P, Geurts JJ. Abundant extracellular myelin in the meninges of patients with multiple sclerosis. Neuropathol Appl Neurobiol 2009; 35: 283-95
5. Calderon TM, Eugenin EA, Lopez L, Kumar SS, Hesselgesser J, Raine CS, Berman JW. A role for CXCL12 (SDF-1alpha) in the pathogenesis of multiple sclerosis: regulation of CXCL12 expression in astrocytes by soluble myelin basic protein. J Neuroimmunol 2006; 177: 27-39
6. Cross AH, Dolich S, Raine CS. Antigen processing of myelin basic protein is required prior to recognition by T cells inducing EAE. Cell Immunol 1990; 129: 22-31
7. D'Souza CA, Moscarello MA. Differences in susceptibility of MBP charge isomers to digestion by stromelysin-1 (MMP-3) and release of an immunodominant epitope. Neurochem Res 2006; 31: 1045-54
8. Mastronardi FG, Moscarello MA. Molecules affecting myelin stability: a novel hypothesis regarding the pathogenesis of multiple sclerosis. J Neurosci Res 2005; 80: 301-8
9. Sajad M, Zargan J, Chawla R, Umar S, Khan HA. Upregulation of CSPG3 accompanies neuronal progenitor proliferation and migration in EAE. J Mol Neurosci 2011; 43: 531-40
10. Zabaleta M, Marino R, Borges J, Camargo B, Ordaz P, De Sanctis JB, Bianco NE. Activity profile in multiple sclerosis: an integrative approach. A preliminary report. Mult Scler 2002; 8: 343-9
11. Reindl M, Linington C, Brehm U, Egg R, Dilitz E, Deisenhammer F, Poewe W, Berger T. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 1999; 122 (Pt 11): 2047-56
12. Belogurov AA Jr, Kurkova IN, Friboulet A, Thomas D, Misikov VK, Zakharova MY, Suchkov SV, Kotov SV, Alehin AI, Avalle B, Souslova EA, Morse HC 3rd, Gabibov AG, Ponomarenko NA. Recognition and degradation of myelin basic protein peptides by serum autoantibodies: novel biomarker for multiple sclerosis. J Immunol 2008; 180: 1258-67
13. Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, Dilitz E, Deisenhammer F, Reindl M. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 2003; 349: 139-45
14. Alvord EC Jr, Hruby S, Shaw CM, Slimp J. Myelin basic protein and its antibodies in the cerebrospinal fluid in experimental allergic encephalomyelitis, multiple sclerosis and other diseases. Prog Clin Biol Res 1984; 146: 359-63
15. Ohta M, Ohta K. Detection of myelin basic protein in cerebrospinal fluid. Expert Rev Mol Diagn 2002; 2: 627-33
16. Thomson AJ, Brazil J, Feighery C, Whelan A, Kellet J, Martin EA, Hutchinson M. CSF myelin basic protein in multiple sclerosis. Acta Neurol Scand 1985; 72: 577-83
17. Gupta MK. Myelin basic protein and demyelinating diseases. Crit Rev Clin Lab Sci 1987; 24: 287-314
18. Vass K, Lassmann H, Wisniewski HM, Iqbal K. Ultracytochemical distribution of myelin basic protein after injection into the cerebrospinal fluid. Evidence for transport through the blood-brain barrier and binding to the luminal surface of cerebral veins. J Neurol Sci 1984; 63: 423-33
19. Luster AD. Chemokines - chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338: 436-45
20. Rollins BJ. Chemokines. Blood 1997; 90: 909-28
21. McManus C, Berman JW, Brett FM, Staunton H, Farrell M, Brosnan CF. MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: an immunohistochemical and in situ hybridization study. J Neuroimmunol 1998; 86: 20-9
22. Simpson JE, Newcombe J, Cuzner ML, Woodroofe MN. Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions. J Neuroimmunol 1998; 84: 238-49
23. Van Der Voorn P, Tekstra J, Beelen RH, Tensen CP, Van Der Valk P, De Groot CJ. Expression of MCP-1 by reactive astrocytes in demyelinating multiple sclerosis lesions. Am J Pathol 1999; 154: 45-51
24. Tanuma N, Sakuma H, Sasaki A, Matsumoto Y. Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis. Acta Neuropathol (Berl) 2006; 112: 195-204
25. Kennedy KJ, Strieter RM, Kunkel SL, Lukacs NW, Karpus WJ. Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1alpha and monocyte chemotactic protein-1. J Neuroimmunol 1998; 92: 98-108
26. Youssef S, Wildbaum G, Karin N. Prevention of experimental autoimmune encephalomyelitis by MIP-1alpha and MCP-1 naked DNA vaccines. J Autoimmun 1999; 13: 21-9
27. Park IK, Hiraki K, Kohyama K, Matsumoto Y. Differential effects of decoy chemokine (7ND) gene therapy on acute, biphasic and chronic autoimmune encephalomyelitis: implication for pathomechanisms of lesion formation. J Neuroimmunol 2008; 194: 34-43
28. Hirano T. Interleukin 6 and its receptor: ten years later. Int Rev Immunol 1998; 16: 249-84
29. Frei K, Malipiero UV, Leist TP, Zinkernagel RM, Schwab ME, Fontana A. On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases. Eur J Immunol 1989; 19: 689-94
30. Cannella B, Raine CS. The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 1995; 37: 424-35
31. Woodroofe MN, Cuzner ML. Cytokine mRNA expression in inflammatory multiple sclerosis lesions: detection by non-radioactive in situ hybridization. Cytokine 1993; 5: 583-8
32. Agnello D, Bigini P, Villa P, Mennini T, Cerami A, Brines ML, Ghezzi P. Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis. Brain Res 2002; 952: 128-34
33. Imler TJ Jr, Petro TM. Decreased severity of experimental autoimmune encephalomyelitis during resveratrol administration is associated with increased IL-17+IL-10+ T cells, CD4(-) IFN-gamma+ cells, and decreased macrophage IL-6 expression. Int Immunopharmacol 2009; 9: 134-43
34. Gijbels K, Brocke S, Abrams JS, Steinman L. Administration of neutralizing antibodies to interleukin-6 (IL-6) reduces experimental autoimmune encephalomyelitis and is associated with elevated levels of IL-6 bioactivity in central nervous system and circulation. Mol Med 1995; 1: 795-805
35. Serada S, Fujimoto M, Mihara M, Koike N, Ohsugi Y, Nomura S, Yoshida H, Nishikawa T, Terabe F, Ohkawara T, Takahashi T, Ripley B, Kimura A, Kishimoto T, Naka T. IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 2008; 105: 9041-6
36. Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008; 57: 178-201
37. Foster CA, Mechtcheriakova D, Storch MK, Balatoni B, Howard LM, Bornancin F, Wlachos A, Sobanov J, Kinnunen A, Baumruker T. FTY720 rescue therapy in the dark agouti rat model of experimental autoimmune encephalomyelitis: expression of central nervous system genes and reversal of blood-brain-barrier damage. Brain Pathol 2009; 19: 254-66
38. Fabis MJ, Scott GS, Kean RB, Koprowski H, Hooper DC. Loss of blood-brain barrier integrity in the spinal cord is common to experimental allergic encephalomyelitis in knockout mouse models. Proc Natl Acad Sci U S A 2007; 104: 5656-61
39. Minagar A, Ostanin D, Long AC, Jennings M, Kelley RE, Sasaki M, Alexander JS. Serum from patients with multiple sclerosis downregulates occludin and VE-cadherin expression in cultured endothelial cells. Mult Scler 2003; 9: 235-8
40. Wuerfel J, Tysiak E, Prozorovski T, Smyth M, Mueller S, Schnorr J, Taupitz M, Zipp F. Mouse model mimics multiple sclerosis in the clinico-radiological paradox. Eur J Neurosci 2007; 26: 190-8
41. Gordon PB, Sussman II, Hatcher VB. Long-term culture of human endothelial cells. In Vitro 1983; 19: 661-71
42. Weiss JM, Downie SA, Lyman WD, Berman JW. Astrocyte-derived monocyte-chemoattractant protein-1 directs the transmigration of leukocytes across a model of the human blood-brain barrier. J Immunol 1998; 161: 6896-903
43. Eugenin EA, Berman JW. Chemokine-dependent mechanisms of leukocyte trafficking across a model of the blood-brain barrier. Methods 2003; 29: 351-61
44. Eugenin EA, Osiecki K, Lopez L, Goldstein H, Calderon TM, Berman JW. CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS. J Neurosci 2006; 26: 1098-106
45. Hurwitz AA, Berman JW, Rashbaum WK, Lyman WD. Human fetal astrocytes induce the expression of blood-brain barrier specific proteins by autologous endothelial cells. Brain Res 1993; 625: 238-43
46. Hochmeister S, Grundtner R, Bauer J, Engelhardt B, Lyck R, Gordon G, Korosec T, Kutzelnigg A, Berger JJ, Bradl M, Bittner RE, Lassmann H. Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis. J Neuropathol Exp Neurol 2006; 65: 855-65
47. Kirk J, Plumb J, Mirakhur M, McQuaid S. Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination. J Pathol 2003; 201: 319-27
48. Morgan L, Shah B, Rivers LE, Barden L, Groom AJ, Chung R, Higazi D, Desmond H, Smith T, Staddon JM. Inflammation and dephosphorylation of the tight junction protein occludin in an experimental model of multiple sclerosis. Neuroscience 2007; 147: 664-73
49. Kieseier BC, Seifert T, Giovannoni G, Hartung HP. Matrix metalloproteinases in inflammatory demyelination: targets for treatment. Neurology 1999; 53: 20-5
50. Yong VW, Zabad RK, Agrawal S, Goncalves Dasilva A, Metz LM. Elevation of matrix metalloproteinases (MMPs) in multiple sclerosis and impact of immunomodulators. J Neurol Sci 2007; 259: 79-84
51. Schulz R. Intracellular targets of matrix metalloproteinase-2 in cardiac disease: rationale and therapeutic approaches. Annu Rev Pharmacol Toxicol 2007; 47: 211-42
52. Pouly S, Antel JP, Ladiwala U, Nalbantoglu J, Becher B. Mechanisms of tissue injury in multiple sclerosis: opportunities for neuroprotective therapy. J Neural Transm Suppl 2000; 58: 193-203
53. Kuhle J, Lindberg RL, Regeniter A, Mehling M, Hoffmann F, Reindl M, Berger T, Radue EW, Leppert D, Kappos L. Antimyelin antibodies in clinically isolated syndromes correlate with inflammation in MRI and CSF. J Neurol 2007; 254: 160-8
54. Cartier L, Hartley O, Dubois-Dauphin M, Krause KH. Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 2005; 48: 16-42
55. Subileau EA, Rezaie P, Davies HA, Colyer FM, Greenwood J, Male DK, Romero IA. Expression of chemokines and their receptors by human brain endothelium: implications for multiple sclerosis. J Neuropathol Exp Neurol 2009; 68: 227-40
56. Frigerio S, Gelati M, Ciusani E, Corsini E, Dufour A, Massa G, Salmaggi A. Immunocompetence of human microvascular brain endothelial cells: cytokine regulation of IL-1beta, MCP-1, IL-10, sICAM-1 and sVCAM-1. J Neurol 1998; 245: 727-30
57. Simpson J, Rezaie P, Newcombe J, Cuzner ML, Male D, Woodroofe MN. Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue. J Neuroimmunol 2000; 108: 192-200
58. Mahad D, Callahan MK, Williams KA, Ubogu EE, Kivisakk P, Tucky B, Kidd G, Kingsbury GA, Chang A, Fox RJ, Mack M, Sniderman MB, Ravid R, Staugaitis SM, Stins MF, Ransohoff RM. Modulating CCR2 and CCL2 at the blood-brain barrier: relevance for multiple sclerosis pathogenesis. Brain 2006; 129: 212-23
59. Sorensen TL, Sellebjerg F. Distinct chemokine receptor and cytokine expression profile in secondary progressive MS. Neurology 2001; 57: 1371-6
60. Fife BT, Huffnagle GB, Kuziel WA, Karpus WJ. CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med 2000; 192: 899-905
61. Huang DR, Wang J, Kivisakk P, Rollins BJ, Ransohoff RM. Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J Exp Med 2001; 193: 713-26
62. Izikson L, Klein RS, Charo IF, Weiner HL, Luster AD. Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J Exp Med 2000; 192: 1075-80
63. Quinones MP, Kalkonde Y, Estrada CA, Jimenez F, Ramirez R, Mahimainathan L, Mummidi S, Choudhury GG, Martinez H, Adams L, Mack M, Reddick RL, Maffi S, Haralambous S, Probert L, Ahuja SK, Ahuja SS. Role of astrocytes and chemokine systems in acute TNFalpha induced demyelinating syndrome: CCR2-dependent signals promote astrocyte activation and survival via NF-kappaB and Akt. Mol Cell Neurosci 2008; 37: 96-109
64. Basso AS, Frenkel D, Quintana FJ, Costa-Pinto FA, Petrovic-Stojkovic S, Puckett L, Monsonego A, Bar-Shir A, Engel Y, Gozin M, Weiner HL. Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. J Clin Invest 2008; 118: 1532-43
65. Dogan RN, Elhofy A, Karpus WJ. Production of CCL2 by central nervous system cells regulates development of murine experimental autoimmune encephalomyelitis through the recruitment of TNF- and iNOS-expressing macrophages and myeloid dendritic cells. J Immunol 2008; 180: 7376-84
66. Malmestrom C, Andersson BA, Haghighi S, Lycke J. IL-6 and CCL2 levels in CSF are associated with the clinical course of MS: implications for their possible immunopathogenic roles. J Neuroimmunol 2006; 175: 176-82
67. Angelucci F, Mirabella M, Caggiula M, Frisullo G, Patanella K, Sancricca C, Nociti V, Tonali PA, Batocchi AP. Evidence of involvement of leptin and IL-6 peptides in the action of interferon-beta in secondary progressive multiple sclerosis. Peptides 2005; 26: 2289-93
68. Wang T, Nagai H, Bouda K, Matsuura S, Takaoka Y, Niwa S, Homma T, Tanaka H, Shudo K. Effect of selective IL-6 inhibitor Am-80 on experimental autoimmune encephalomyelitis in DA rats. Acta Pharmacol Sin 2000; 21: 967-76
69. Okuda Y, Sakoda S, Bernard CC, Fujimura H, Saeki Y, Kishimoto T, Yanagihara T. IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein. Int Immunol 1998; 10: 703-8
70. Harrington LE, Mangan PR, Weaver CT. Expanding the effector CD4 T-cell repertoire: the Th17 lineage. Curr Opin Immunol 2006; 18: 349-56
71. Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N, Becher B, Prat A. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 2007; 13: 1173-5
72. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005; 201: 233-40
73. McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23-IL-17 immune pathway. Trends Immunol 2006; 27: 17-23
74. Mestre L, Correa F, Docagne F, Clemente D, Guaza C. The synthetic cannabinoid WIN 55, 212-2 increases COX-2 expression and PGE2 release in murine brain-derived endothelial cells following Theiler's virus infection. Biochem Pharmacol 2006; 72: 869-80
75. Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol 2004; 63: 901-10
76. Rose JW, Hill KE, Watt HE, Carlson NG. Inflammatory cell expression of cyclooxygenase-2 in the multiple sclerosis lesion. J Neuroimmunol 2004; 149: 40-9
77. Cao C, Matsumura K, Shirakawa N, Maeda M, Jikihara I, Kobayashi S, Watanabe Y. Pyrogenic cytokines injected into the rat cerebral ventricle induce cyclooxygenase-2 in brain endothelial cells and also upregulate their receptors. Eur J Neurosci 2001; 13: 1781-90
78. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. Cyclooxygenase in biology and disease. FASEB J 1998; 12: 1063-73
79. Mark KS, Trickler WJ, Miller DW. Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. J Pharmacol Exp Ther 2001; 297: 1051-8
80. Paintlia AS, Paintlia MK, Singh I, Singh AK. IL-4-induced peroxisome proliferator-activated receptor gamma activation inhibits NF-kappaB trans activation in central nervous system (CNS) glial cells and protects oligodendrocyte progenitors under neuroinflammatory disease conditions: implication for CNS-demyelinating diseases. J Immunol 2006; 176: 4385-98
81. Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Mult Scler 2003; 9: 540-9
82. Petty MA, Lo EH. Junctional complexes of the blood-brain barrier: permeability changes in neuroinflammation. Prog Neurobiol 2002; 68: 311-23
83. Bolton C, Paul C. Glutamate receptors in neuroinflammatory demyelinating disease. Mediators Inflamm 2006; 2006: 93684
84. Encinas JM, Manganas L, Enikolopov G. Nitric oxide and multiple sclerosis. Curr Neurol Neurosci Rep 2005; 5: 232-8
85. Kean RB, Spitsin SV, Mikheeva T, Scott GS, Hooper DC. The peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the central nervous system in experimental allergic encephalomyelitis through maintenance of blood-central nervous system barrier integrity. J Immunol 2000; 165: 6511-18
86. Paul C, Bolton C. Modulation of blood-brain barrier dysfunction and neurological deficits during acute experimental allergic encephalomyelitis by the N-methyl-D-aspartate receptor antagonist memantine. J Pharmacol Exp Ther 2002; 302: 50-7
87. Furuse M, Sasaki H, Tsukita S. Manner of interaction of heterogeneous claudin species within and between tight junction strands. J Cell Biol 1999; 147: 891-903
88. Hirase T, Staddon JM, Saitou M, Ando-Akatsuka Y, Itoh M, Furuse M, Fujimoto K, Tsukita S, Rubin LL. Occludin as a possible determinant of tight junction permeability in endothelial cells. J Cell Sci 1997; 110 (Pt 14): 1603-13
89. Kermode AG, Thompson AJ, Tofts P, MacManus DG, Kendall BE, Kingsley DP, Moseley IF, Rudge P, McDonald WI. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain 1990; 113 (Pt 5): 1477-89
90. Plumb J, McQuaid S, Mirakhur M, Kirk J. Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis. Brain Pathol 2002; 12: 154-69
91. Pfeiffer F, Schafer J, Lyck R, Makrides V, Brunner S, Schaeren-Wiemers N, Deutsch U, Engelhardt B. Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis. Acta Neuropathol (Berl) 2011; 122: 601-14
92. Dong M, Liu R, Guo L, Li C, Tan G. Pathological findings in rats with experimental allergic encephalomyelitis. APMIS 2008; 116: 972-84
93. Clements JM, Cossins JA, Wells GM, Corkill DJ, Helfrich K, Wood LM, Pigott R, Stabler G, Ward GA, Gearing AJ, Miller KM. Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumour necrosis factor-alpha inhibitor. J Neuroimmunol 1997; 74: 85-94
94. Gijbels K, Galardy RE, Steinman L. Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteases. J Clin Invest 1994; 94: 2177-82
95. Hewson AK, Smith T, Leonard JP, Cuzner ML. Suppression of experimental allergic encephalomyelitis in the Lewis rat by the matrix metalloproteinase inhibitor Ro31-9790. Inflamm Res 1995; 44: 345-9
96. Gaultier A, Wu X, Le Moan N, Takimoto S, Mukandala G, Akassoglou K, Campana WM, Gonias SL. Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis. J Cell Sci 2009; 122: 1155-62
97. Wolf BB, Lopes MB, VandenBerg SR, Gonias SL. Characterization and immunohistochemical localization of alpha 2-macroglobulin receptor (low-density lipoprotein receptor-related protein) in human brain. Am J Pathol 1992; 141: 37-42
98. Yu G, Rux AH, Ma P, Bdeir K, Sachais BS. Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-kappaB-dependent manner. Blood 2005; 105: 3545-51
99. Yepes M, Sandkvist M, Moore EG, Bugge TH, Strickland DK, Lawrence DA. Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. J Clin Invest 2003; 112: 1533-40