1. Academic Validation
  2. Monocyte migration and LFA-1-mediated attachment to brain microvascular endothelia is regulated by SDF-1 alpha through Lyn kinase

Monocyte migration and LFA-1-mediated attachment to brain microvascular endothelia is regulated by SDF-1 alpha through Lyn kinase

  • J Immunol. 2008 Oct 1;181(7):4632-7. doi: 10.4049/jimmunol.181.7.4632.
Mobeen Malik 1 Ying-Yu Chen Martha F Kienzle Brian E Tomkowicz Ronald G Collman Andrzej Ptasznik
Affiliations

Affiliation

  • 1 Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA.
Abstract

Infiltration of activated monocytes into the brain is a prerequisite for the development of various neurological disorders such as HIV-associated dementia, multiple sclerosis, and Other inflammatory processes. In these pathologies, the chemokine SDF-1alpha (CXCL12) is over-expressed and might attract monocytes into the CNS. We demonstrate here that SDF-1alpha stimulates migration of monocytes through its receptor, CXCR4, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta(2) integrins. SDF-1alpha also decreases monocyte adherence to brain microvascular endothelial cells (BMVEC) that are activated with TNF-alpha, IL-1beta, or recombinant envelope glycoprotein from HIV-1, which increase BMVEC expression of ICAM-1. The decreased adherence is linked to down-regulation on monocytes of the activation-dependent epitope of the beta(2) Integrin LFA-1 by SDF-1alpha. Knockdown of Lyn in monocytes using small interfering RNA decreases SDF-1alpha-mediated migration and prevents the inhibition of monocyte attachment to ICAM-1 and activated BMVEC. Thus, in SDF-1alpha-stimulated monocytes, Lyn acts as a positive regulator of migration and a negative regulator of adhesion to BMVEC through the LFA-1 Integrin. These results provide a novel Lyn-mediated signaling mechanism for the regulation of monocyte movement at the blood-brain barrier.

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