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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chen, Ying-Yu Collman, Ronald G. Tomkowicz, Brian E. Malik, Mobeen Kienzle, Martha F. Ptasznik, Andrzej
Description	Country affiliation: United States Author Affiliation: Malik M ( 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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	181
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2008-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Blood Supply Chemokine Cxcl12 Physiology Chemotaxis, Leukocyte Immunology Endothelium, Vascular Cytology Lymphocyte Function-associated Antigen-1 Monocytes Src-family Kinases Antigens, Cd18 Metabolism Enzymology Cell Adhesion Cell Migration Inhibition Down-regulation Intercellular Adhesion Molecule-1 Biosynthesis Genetics Ligands Microcirculation Receptors, Cxcr4 Signal Transduction Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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

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