Extracellular matrix in multiple sclerosis lesions: Fibrillar collagens, biglycan and decorin are upregulated and associated with infiltrating immune cells.
Extracellular matrix (ECM) proteins can modify immune reactions, e.g. by sequestering or displaying growth factors and by interacting with immune and glial cells. Here we quantified by quantitative polymerase chain reaction (qPCR) expression of 50 ECM components and 34 ECM degrading enzymes in multiple sclerosis (MS) active and inactive white matter lesions. COL1A1, COL3A1, COL5A1 and COL5A2 chains were induced strongly in active lesions and even more in inactive lesions. These chains interact to form collagen types I, III and V, which are fibrillar collagens. Biglycan and decorin, which can decorate fibrillar collagens, were also induced strongly. The fibrillar collagens, biglycan and decorin were largely found between the endothelium and astrocytic glia limitans in the perivascular space where they formed a meshwork which was closely associated with infiltrating immune cells. In active lesions collagen V was also seen in the heavily infiltrated parenchyma. Fibrillar collagens I and III inhibited in vitro human monocyte production of CCL2 (MCP-1), an inflammatory chemokine involved in recruitment of immune cells. Together, ECM changes in lesions with different activities were quantified and proteins forming a perivascular fibrosis were identified. Induced fibrillar collagens may contribute to limiting enlargement of MS lesions by inhibiting the production of CCL2 by monocytes.
Mohan
Hema
H
Institute for Clinical Neuroimmunology, Ludwig Maximilians University, Munich, Germany.
Krumbholz
Markus
M
Sharma
Rakhi
R
Eisele
Sylvia
S
Junker
Andreas
A
Sixt
Michael
M
Newcombe
Jia
J
Wekerle
Hartmut
H
Hohlfeld
Reinhard
R
Lassmann
Hans
H
Meinl
Edgar
E
D058578:Biglycan / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D058575:Decorin / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005109:Extracellular Matrix / Q000473:pathology*; D024022:Fibrillar Collagens / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009103:Multiple Sclerosis / Q000473:pathology*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology*
D058578:Biglycan; D018925:Chemokines; D024042:Collagen Type I; D058575:Decorin; D024022:Fibrillar Collagens; D011509:Proteoglycans; D012333:RNA, Messenger
J Cell Biol. 1997 Feb 10;136(3):729-43
9024701
Biochem Biophys Res Commun. 2009 May 1;382(2):341-7
19281798
J Neurochem. 2007 Nov;103(4):1293-301
17854386
J Neuropathol Exp Neurol. 1996 Dec;55(12):1194-204
8957442
J Neuropathol Exp Neurol. 1970 Jan;29(1):6-20
5411623
J Neuropathol Exp Neurol. 2001 Dec;60(12):1198-207
11764092
N Engl J Med. 2006 Feb 9;354(6):610-21
16467548
Acta Neuropathol. 1993;86(3):224-35
8213080
Blood. 2002 Aug 15;100(4):1160-7
12149192
Neuropathol Appl Neurobiol. 1997 Oct;23(5):406-15
9364466
Anat Embryol (Berl). 1993 Nov;188(5):419-33
7508695
J Biol Chem. 2009 Aug 21;284(34):23001-11
19542530
J Biol Chem. 2004 Sep 3;279(36):37368-76
15226297
Nat Med. 2009 May;15(5):519-27
19396173
J Neuropathol Exp Neurol. 1996 Mar;55(3):300-9
8786388
J Neurol Sci. 1991 Jan;101(1):59-72
2027028
J Immunol. 2000 Dec 1;165(11):6576-82
11086101
Neurosci Res. 2007 Aug;58(4):371-7
17669534
FASEB J. 1991 Oct;5(13):2814-23
1916105
Am J Pathol. 2001 Feb;158(2):345-53
11159170
Am J Pathol. 1989 Jul;135(1):161-8
2528301
Brain. 2008 Sep;131(Pt 9):2332-40
18676439
J Exp Med. 2006 Apr 17;203(4):1007-19
16585265
J Cell Sci. 2007 Jun 15;120(Pt 12):1955-8
17550969
Trends Mol Med. 2006 Oct;12(10):488-96
16962376
Trends Cell Biol. 2008 Nov;18(11):560-74
18848450
Cell Mol Life Sci. 2000 Feb;57(2):276-89
10766023
Cell Tissue Res. 2002 Oct;310(1):19-29
12242480
J Biol Chem. 1999 Jul 2;274(27):18843-6
10383378
Arch Biochem Biophys. 2000 Feb 1;374(1):24-34
10640392
J Neuropathol Exp Neurol. 1995 Mar;54(2):202-13
7533209
J Exp Med. 2001 Mar 19;193(6):713-26
11257138
Rev Esp Cardiol. 2006 Oct;59(10):1047-57
17125715
Neuropathol Appl Neurobiol. 2006 Dec;32(6):585-93
17083473
Semin Immunol. 2003 Feb;15(1):23-32
12495638
Int Immunol. 1995 Sep;7(9):1489-95
7495756
Trends Neurosci. 2008 Jan;31(1):44-52
18063497
J Clin Invest. 2007 Nov;117(11):3306-15
17965773
J Neurosci Res. 1997 Nov 15;50(4):539-48
9404716
J Cell Biol. 1990 Mar;110(3):767-75
2137829
J Clin Neurosci. 2000 Jul;7(4):280-90
10938601
Nat Med. 2005 Sep;11(9):966-72
16086023
J Neuropathol Exp Neurol. 2005 Aug;64(8):722-9
16106221
Nat Rev Neurosci. 2001 Jul;2(7):502-11
11433375
FASEB J. 2004 May;18(7):816-27
15117886
J Neuropathol Exp Neurol. 2008 Dec;67(12):1113-21
19018243
Glia. 2003 Mar;41(4):382-92
12555205
Cell Mol Life Sci. 2004 Aug;61(16):2031-45
15316653
Neuropathol Appl Neurobiol. 1999 Jun;25(3):207-14
10417662
J Biol Chem. 2002 Nov 15;277(46):43707-16
12221095
Physiol Rev. 2000 Oct;80(4):1267-90
11015614
Acta Neuropathol. 2000 Sep;100(3):245-52
10965793
Nature. 2008 Feb 28;451(7182):1076-81
18278032
Neuron. 2004 Dec 16;44(6):961-75
15603739
J Clin Invest. 2005 Aug;115(8):2223-33
16025156
J Neurosurg. 1988 Aug;69(2):155-70
3292716
J Biol Chem. 2002 Apr 12;277(15):12921-30
11821431