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

Area of Science:

• Neuroimmunology
• Cellular and Molecular Neuroscience
• Vascular Biology

Background:

• Leukocyte trafficking into the central nervous system (CNS) is critical in neuroinflammatory diseases.
• Adhesion molecules of the immunoglobulin superfamily mediate leukocyte migration across the blood-brain barrier (BBB).

Purpose of the Study:

• To identify novel adhesion molecules involved in leukocyte extravasation across the BBB.
• To investigate the role of ALCAM in leukocyte recruitment to the CNS and its potential as a therapeutic target.

Main Methods:

• Lipid raft-based proteomic analysis to identify adhesion molecules.
• Immunofluorescence microscopy to visualize ALCAM localization on BBB endothelium and in transmigratory cups.
• In vitro and in vivo models to assess the effect of ALCAM blockade on leukocyte transmigration and experimental autoimmune encephalomyelitis (EAE) severity.

Main Results:

• ALCAM was identified as an adhesion molecule mediating leukocyte migration across the BBB.
• ALCAM expression was upregulated on BBB cells in active multiple sclerosis and EAE lesions.
• ALCAM blockade inhibited CD4+ lymphocyte and monocyte transmigration across the BBB in vitro and in vivo.
• ALCAM blockade reduced EAE severity and delayed disease onset.

Conclusions:

• ALCAM plays a significant role in leukocyte recruitment to the brain.
• ALCAM represents a potential therapeutic target for dampening neuroinflammation in diseases like multiple sclerosis.