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

Nat Immunol. 2008 Feb;9(2):137-45. doi: 10.1038/ni1551. Epub 2007 Dec 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule / analysis
  • Activated-Leukocyte Cell Adhesion Molecule / drug effects
  • Activated-Leukocyte Cell Adhesion Molecule / metabolism*
  • Blood-Brain Barrier / chemistry
  • Blood-Brain Barrier / metabolism*
  • Brain / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Movement* / drug effects
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Humans
  • Membrane Microdomains / chemistry
  • Membrane Microdomains / metabolism
  • Proteomics


  • Activated-Leukocyte Cell Adhesion Molecule