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

Nat Immunol. 2008 Feb; 9(2):137-45.

Speaker: 蔡明勳                    Time: 13:00-14:00, 03/05, 2008

Commentator: 陳舜華 老師           Place: Room 601

Abstract

   The blood-brain barrier (BBB) is a semi-permeable membranic structure formed by brain capillary endothelial cells. It protects the brain from the many harmful chemicals, toxins, and infectious agents within the blood. When CNS infection, activated immune cells can cross the intact BBB. These cells must share an ability to recognize and bind to brain ECs and then initiate junction-opening mechanisms. However, the entry and proliferation of myelin-reactive leukocytes is thought to be the cause of multiple sclerosis (MS). To study leukocytes infiltrate through BBB to CNS, the authors identified an adhesion molecule - activated leukocyte cell adhesion molecule (ALCAM) expressed dominant on lipid raft of BBB endothelial cells. Then, they found ALCAM expression could up-regulate by inflammatory cytokines such as TNF-alpha and IFN-gamma. To investigate the association of ALCAM expression and clinical CNS damaging, they compared ALCAM expression in MS lesion with in normal appearing white matter. The ALCAM expression was greater in MS lesion. In addition, the same result was observed in EAE - an animal model of MS. MS and EAE are both inflammating and demyelinating CNS diseasees, and associated with immune cells infiltration and changed BBB permeability. To block ALCAM in EAE mice model, they found that ALCAM blockage could retard the progression and reduce the severity of EAE. Moreover, fewer inflammation lesions and leukocyte infiltration in EAE mice treated with ALCAM-blocking antibody. By modified Boyden chamber assay, they also found that ALCAM blockade restricted human leukocytes, including CD4^＋ ,CD19⁺ , and CD14⁺ leukocytes, across BBB endothelial cells. Finally, they demonstrated that both ALCAM and ICAM-1 play important and partially redundant functions in leukocyte transmigration across BBB endothelial cells, and could be considered as therapeutic targets.

Reference：

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