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CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation

CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation
CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation
Perivascular macrophages (PVM) constitute a subpopulation of resident macrophages in the central nervous system (CNS) that by virtue of their strategic location at the blood-brain barrier potentially lend themselves to a variety of important functions in both health and disease. Functional evidence suggests that PVM play a supportive role during experimental autoimmune encephalomyelitis in rodents. However, the function of PVM in the human CNS remains poorly characterized. We first set out to investigate the validity of the antibody EDhu1, which recognizes human CD163, to specifically identify human PVM. Second, we wanted to gain insight into the function of PVM in antigen recognition and presentation and therefore we studied the expression of DC-SIGN, mannose receptor, MHC class II, and several costimulatory molecules by PVM in the normal and inflamed human CNS (multiple sclerosis (MS) brain lesions). Conventional immunohistochemistry and double-labeled immunofluorescence techniques were used. We show that CD163 specifically reveals PVM in the normal human CNS. In MS lesions, CD163 staining reveals expression on foamy macrophages and microglia, besides an upregulation of the amount of PVM stained. In contrast, mannose receptor expression is restricted to PVM in both normal and inflamed brain tissue. Furthermore, we show that a subpopulation of PVM in the human brain express several molecules involved in antigen recognition, presentation, and costimulation. Therefore PVM, which occupy a strategic location at the BBB, are equipped to recognize antigen and present it to T cells, supporting a role in the regulation of perivascular inflammation in the human CNS.
antigen presentation and recognition, costimulatory molecules, multiple sclerosis, dc-sign, perivascular macrophages, mannose receptor
0894-1491
297-305
Fabriek, Babs O.
5803127a-a6d9-408a-9832-6b5d07bd1caa
Van Haastert, Elise S.
31e889d3-8168-4f24-932c-410db2156a50
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Polfliet, Machteld M.J.
c6a743dc-3464-41a8-802b-f9dbe2360684
Dopp, Ed D.
813b6bee-9c72-4003-a006-f839acf343d2
Van den Heuvel, Michel M.
41f4ed13-6fdb-4411-9f0d-1d421b318123
Van den Berg, Timo K.
8750eb78-7418-4d8e-9c20-b7137924b6d6
de Groot, Corline J.A.
1d0e0c6e-d43e-4a9f-bafc-ba5f60c5a4f3
Van der Valk, Paul
1ab1fe18-6dda-4d0f-be9f-22803100fd35
Dijkstra, Christine D.
656a7fb9-fa07-458c-80d9-e7aa33f48a72
Fabriek, Babs O.
5803127a-a6d9-408a-9832-6b5d07bd1caa
Van Haastert, Elise S.
31e889d3-8168-4f24-932c-410db2156a50
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Polfliet, Machteld M.J.
c6a743dc-3464-41a8-802b-f9dbe2360684
Dopp, Ed D.
813b6bee-9c72-4003-a006-f839acf343d2
Van den Heuvel, Michel M.
41f4ed13-6fdb-4411-9f0d-1d421b318123
Van den Berg, Timo K.
8750eb78-7418-4d8e-9c20-b7137924b6d6
de Groot, Corline J.A.
1d0e0c6e-d43e-4a9f-bafc-ba5f60c5a4f3
Van der Valk, Paul
1ab1fe18-6dda-4d0f-be9f-22803100fd35
Dijkstra, Christine D.
656a7fb9-fa07-458c-80d9-e7aa33f48a72

Fabriek, Babs O., Van Haastert, Elise S., Galea, Ian, Polfliet, Machteld M.J., Dopp, Ed D., Van den Heuvel, Michel M., Van den Berg, Timo K., de Groot, Corline J.A., Van der Valk, Paul and Dijkstra, Christine D. (2005) CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation. Glia, 51 (4), 297-305. (doi:10.1002/glia.20208).

Record type: Article

Abstract

Perivascular macrophages (PVM) constitute a subpopulation of resident macrophages in the central nervous system (CNS) that by virtue of their strategic location at the blood-brain barrier potentially lend themselves to a variety of important functions in both health and disease. Functional evidence suggests that PVM play a supportive role during experimental autoimmune encephalomyelitis in rodents. However, the function of PVM in the human CNS remains poorly characterized. We first set out to investigate the validity of the antibody EDhu1, which recognizes human CD163, to specifically identify human PVM. Second, we wanted to gain insight into the function of PVM in antigen recognition and presentation and therefore we studied the expression of DC-SIGN, mannose receptor, MHC class II, and several costimulatory molecules by PVM in the normal and inflamed human CNS (multiple sclerosis (MS) brain lesions). Conventional immunohistochemistry and double-labeled immunofluorescence techniques were used. We show that CD163 specifically reveals PVM in the normal human CNS. In MS lesions, CD163 staining reveals expression on foamy macrophages and microglia, besides an upregulation of the amount of PVM stained. In contrast, mannose receptor expression is restricted to PVM in both normal and inflamed brain tissue. Furthermore, we show that a subpopulation of PVM in the human brain express several molecules involved in antigen recognition, presentation, and costimulation. Therefore PVM, which occupy a strategic location at the BBB, are equipped to recognize antigen and present it to T cells, supporting a role in the regulation of perivascular inflammation in the human CNS.

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Published date: September 2005
Keywords: antigen presentation and recognition, costimulatory molecules, multiple sclerosis, dc-sign, perivascular macrophages, mannose receptor

Identifiers

Local EPrints ID: 68606
URI: https://eprints.soton.ac.uk/id/eprint/68606
ISSN: 0894-1491
PURE UUID: 05bf912c-78e2-4a54-a7d2-0a5258d59764
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

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Date deposited: 10 Sep 2009
Last modified: 06 Jun 2018 12:46

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Contributors

Author: Babs O. Fabriek
Author: Elise S. Van Haastert
Author: Ian Galea ORCID iD
Author: Machteld M.J. Polfliet
Author: Ed D. Dopp
Author: Michel M. Van den Heuvel
Author: Timo K. Van den Berg
Author: Corline J.A. de Groot
Author: Paul Van der Valk
Author: Christine D. Dijkstra

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