AI Article Synopsis

  • ALCAM is a cell adhesion molecule located on blood-brain barrier endothelial cells that plays a role in controlling the movement of immune cells across the barrier.
  • In a study using ALCAM knockout mice, it was found that these mice developed a more severe form of experimental autoimmune encephalomyelitis (EAE), showing an increase in proinflammatory immune cell infiltration into the central nervous system compared to wild-type mice.
  • The research indicates that ALCAM is crucial for maintaining the integrity of the blood-brain barrier by contributing to the assembly of tight junction molecules, which helps prevent excessive permeability of blood vessels in the central nervous system.

Article Abstract

Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule found on blood-brain barrier endothelial cells (BBB-ECs) that was previously shown to be involved in leukocyte transmigration across the endothelium. In the present study, we found that ALCAM knockout (KO) mice developed a more severe myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). The exacerbated disease was associated with a significant increase in the number of CNS-infiltrating proinflammatory leukocytes compared with WT controls. Passive EAE transfer experiments suggested that the pathophysiology observed in active EAE was linked to the absence of ALCAM on BBB-ECs. In addition, phenotypic characterization of unimmunized ALCAM KO mice revealed a reduced expression of BBB junctional proteins. Further in vivo, in vitro, and molecular analysis confirmed that ALCAM is associated with tight junction molecule assembly at the BBB, explaining the increased permeability of CNS blood vessels in ALCAM KO animals. Collectively, our data point to a biologically important function of ALCAM in maintaining BBB integrity.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278491PMC
http://dx.doi.org/10.1073/pnas.1614336114DOI Listing

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