Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system

被引：331

作者：

Cayrol, Romain ^{[1
]}

Wosik, Karolina ^{[1
]}

Berard, Jennifer L. ^{[2
]}

Dodelet-Devillers, Aurore ^{[1
]}

Ifergan, Igal ^{[1
]}

Kebir, Hania ^{[1
]}

Haqqani, Arsalan S. ^{[3
]}

Kreymborg, Katharina ^{[4
]}

Krug, Sebastian ^{[1
]}

Moumdjian, Robert ^{[5
]}

Bouthillier, Alain ^{[5
]}

Becher, Burkhard ^{[4
]}

Arbour, Nathalie ^{[1
]}

David, Samuel ^{[2
]}

Stanimirovic, Danica ^{[3
]}

Prat, Alexandre ^{[1
,6
]}

机构：

[1] Univ Montreal, Notre Dame Hosp, Ctr Hosp, Ctr Excellence Neurom,Neuroimmunol Res Lab, Montreal, PQ H2L 4M1, Canada

[2] McGill Univ, Ctr Hlth, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada

[3] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada

[4] Univ Zurich, Neuroimmunol Div, CH-8057 Zurich, Switzerland

[5] Univ Montreal, Notre Dame Hosp, Ctr Hosp, Dept Neurosurg, Montreal, PQ H2L 4M1, Canada

[6] Univ Montreal, Notre Dame Hosp, Ctr Hosp, Dept Neurol,Multiple Sclerosis Clin, Montreal, PQ H2L 4M1, Canada

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 02期

基金：

加拿大创新基金会; 加拿大健康研究院;

关键词：

D O I：

10.1038/ni1551

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 [免疫学];

摘要：

Adhesion molecules of the immunoglobulin superfamily are crucial effectors of leukocyte trafficking into the central nervous system. Using a lipid raft-based proteomic approach, we identified ALCAM as an adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM expressed on BBB endothelium localized together with CD6 on leukocytes and with BBB endothelium transmigratory cups. ALCAM expression on BBB cells was upregulated in active multiple sclerosis and experimental autoimmune encephalomyelitis lesions. Moreover, ALCAM blockade restricted the transmigration of CD4(+) lymphocytes and monocytes across BBB endothelium in vitro and in vivo and reduced the severity and delayed the time of onset of experimental autoimmune encephalomyelitis. Our findings indicate an important function for ALCAM in the recruitment of leukocytes into the brain and identify ALCAM as a potential target for the therapeutic dampening of neuroinflammation.

引用

页码：137 / 145

页数：9

共 48 条

[1]

Cross-linking of brain endothelial intercellular adhesion molecule (ICAM)-1 induces association of ICAM-1 with detergent-insoluble cytoskeletal fraction [J].