ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood-brain barrier

作者：Lyck Ruth^*; Lecuyer Marc Andre; Abadier Michael; Wyss Christof B; Matti Christoph; Rosito Maria; Enzmann Gaby; Zeis Thomas; Michel Laure; Martin Ana B Garcia; Sallusto Federica; Gosselet Fabien; Deutsch Urban; Weiner Joshua A; Schaeren Wiemers Nicole; Prat Alexandre; Engelhardt Britta

来源：Journal of Cerebral Blood Flow and Metabolism, 2017, 37(8): 2894-2909.

DOI：10.1177/0271678X16678639

• ALCAM
• blood-brain barrier
• immune cell extravasation
• multiple sclerosis
• neuroinflammation

Activated leukocyte cell adhesion molecule (ALCAM) has been proposed to mediate leukocyte migration across the blood-brain barrier (BBB) in multiple sclerosis or experimental autoimmune encephalomyelitis (EAE). Here, we confirmed vascular ALCAM expression in human brain tissue samples in situ and on two different human in vitro BBB models. Antibody-mediated inhibition of ALCAM reduced diapedesis of human CD4(+) Th1 but not of Th17 cells across the human BBB in vitro. In accordance to human Th1 cells, mouse Th1 cells showed reduced diapedesis across an ALCAM(-/-) in vitro BBB model under static but no longer under flow conditions. In contrast to the limited role of ALCAM in T cell extravasation across the BBB, we found a contribution of ALCAM to rolling, adhesion, and diapedesis of human CD14(+) monocytes across the human BBB under flow and static conditions. Taken together, our study highlights the potential differences in the CNS expression of ALCAM in mouse and human and supports a prominent role for ALCAM in the multi-step extravasation of monocytes across the BBB.

• 出版日期2017-8