Linked Life Data

21508219

Source:http://linkedlifedata.com/resource/pubmed/id/21508219

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2011-4-21
pubmed:abstractText
Human immunodeficiency virus (HIV)-associated increase in monocyte adhesion and trafficking is exacerbated by cocaine abuse. The underlying mechanisms involve cocaine-mediated upregulation of adhesion molecules with subsequent disruption of the blood-brain barrier (BBB). Recently, a novel activated leukocyte cell adhesion molecule (ALCAM) has been implicated in leukocyte transmigration across the endothelium. We now show that upregulation of ALCAM in the brain endothelium seen in HIV(+)/cocaine drug abusers paralleled increased CD68 immunostaining compared with HIV(+)/no cocaine or uninfected controls, suggesting the important role of ALCAM in promoting leukocyte infiltration across the BBB. Furthermore, ALCAM expression was increased in cocaine-treated mice with concomitant increase in monocyte adhesion and transmigration in vivo, which was ameliorated by pretreating with the neutralizing antibody to ALCAM, lending additional support to the role of ALCAM. This new concept was further confirmed by in vitro experiments. Cocaine-mediated induction of ALCAM in human brain microvascular endothelial cells through the translocation of ? receptor to the plasma membrane, followed by phosphorylation of PDGF-? (platelet-derived growth factor-?) receptor. Downstream activation of mitogen-activated protein kinases, Akt, and NF-?B (nuclear factor-?B) pathways resulted in induced expression of ALCAM. Functional implication of upregulated ALCAM was confirmed using cell adhesion and transmigration assays. Neutralizing antibody to ALCAM ameliorated this effect. Together, these findings implicate cocaine-mediated induction of ALCAM as a mediator of increased monocyte adhesion/transmigration into the CNS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5942-55
pubmed:meshHeading
pubmed-meshheading:21508219-Activated-Leukocyte Cell Adhesion Molecule, pubmed-meshheading:21508219-Animals, pubmed-meshheading:21508219-Blood-Brain Barrier, pubmed-meshheading:21508219-Brain, pubmed-meshheading:21508219-Cell Adhesion, pubmed-meshheading:21508219-Cell Movement, pubmed-meshheading:21508219-Cells, Cultured, pubmed-meshheading:21508219-Chromatin Immunoprecipitation, pubmed-meshheading:21508219-Cocaine, pubmed-meshheading:21508219-Cocaine-Related Disorders, pubmed-meshheading:21508219-Flow Cytometry, pubmed-meshheading:21508219-Fluorescence Resonance Energy Transfer, pubmed-meshheading:21508219-HIV Infections, pubmed-meshheading:21508219-Humans, pubmed-meshheading:21508219-Male, pubmed-meshheading:21508219-Mice, pubmed-meshheading:21508219-Mice, Inbred C57BL, pubmed-meshheading:21508219-Mice, Nude, pubmed-meshheading:21508219-Monocytes, pubmed-meshheading:21508219-NF-kappa B, pubmed-meshheading:21508219-Receptors, sigma, pubmed-meshheading:21508219-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2011
pubmed:articleTitle
Cocaine hijacks ?1 receptor to initiate induction of activated leukocyte cell adhesion molecule: implication for increased monocyte adhesion and migration in the CNS.
pubmed:affiliation
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural