Proteolytic shedding of the macrophage scavenger receptor CD163 in multiple sclerosis.
The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP) resulting in soluble CD163 (sCD163). In the present report the shedding of CD163 was investigated in multiple sclerosis (MS). An upregulation of plasma sCD163 and a down regulation of membrane CD163 in MS patients compared to healthy controls was observed. The levels of plasma sCD163 correlated with plasma MMP-9 levels in controls, but not in MS patients. Moreover, evidence was obtained for CD163-cleaving MMP activity in plasma of MS patients. Finally, the increased proteolytic shedding of CD163 correlated to reduced plasma levels of circulating inflammatory cytokines. Collectively, our results provide evidence for proteolytic shedding of CD163 in MS and suggest a possible link to cytokine production.
Fabriek
Babs O
BO
Department of Molecular Cell Biology and Immunology, VU Medical Center, The Netherlands.
Møller
Holger J
HJ
Vloet
Rianka P M
RP
van Winsen
Lisa M
LM
Hanemaaijer
Roeland
R
Teunissen
Charlotte E
CE
Uitdehaag
Bernard M J
BM
van den Berg
Timo K
TK
Dijkstra
Christine D
CD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000097:blood* / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood* / Q000276:immunology*; D002461:Cell Line, Transformed; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000097:blood* / Q000276:immunology*; D018709:Statistics, Nonparametric; D014162:Transfection / Q000379:methods; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D016207:Cytokines; D004791:Enzyme Inhibitors; D011956:Receptors, Cell Surface; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006854:Hydrocortisone