Linked Life Data

15481136

Source:http://linkedlifedata.com/resource/pubmed/id/15481136

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2004-10-14
pubmed:abstractText
CD16+ monocytes represent 5-10% of circulating monocytes in healthy individuals and are dramatically expanded in several pathological conditions including AIDS and HIV-1-associated dementia (HAD). CD16+ monocytes constitutively produce high levels of pro-inflammatory cytokines and neurotoxic factors that may contribute to the pathogenesis of these disorders. Monocyte recruitment into the central nervous system (CNS) and other peripheral tissues in response to locally produced chemokines is a critical event in immune surveillance and inflammation and involves monocyte arrest onto vascular beds and subsequent diapedesis. Here we investigate the ability of CD16+ monocytes to undergo transendothelial migration (TEM) under constitutive and inflammatory conditions. CD16+ monocytes underwent TEM across unstimulated human umbilical vascular (HUVEC) and brain microvascular endothelial (BMVEC) cell monolayers in response to soluble fractalkine (FKN/CX3CL1). Stimulation with tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) induced high and low expression of membrane-bound FKN on HUVEC and BMVEC, respectively, together with expression of VCAM-1 and intercellular adhesion molecule-1 (ICAM)-1. By contrast, only HUVEC expressed CD62E while BMVEC remained negative. Both CD16- and CD16+ monocyte subsets adhered to TNF/IFN-gamma-stimulated HUVEC with higher frequency than to unstimulated HUVEC. Monocyte chemoattractant protein-1 (MCP-1) triggered efficient TEM of CD16- monocytes across TNF/IFN-gamma-stimulated HUVEC, whereas soluble FKN failed to induce TEM of CD16+ monocytes across stimulated HUVEC. These results demonstrate that stimulation with TNF and IFN-gamma triggers expression of membrane-bound FKN on both HUVEC and BMVEC, but prevents TEM of CD16+ monocytes in response to soluble FKN. Thus, pro-inflammatory CD16+ monocytes may contribute to the pathogenesis of HAD and other inflammatory CNS diseases by affecting the integrity of the blood-brain barrier as a consequence of their massive accumulation onto inflamed brain vascular endothelial cells expressing FKN and other adhesion molecules.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0171-2985
pubmed:author
pubmed:issnType
Print
pubmed:volume
209
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11-20
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15481136-Brain, pubmed-meshheading:15481136-Cell Adhesion, pubmed-meshheading:15481136-Cell Adhesion Molecules, pubmed-meshheading:15481136-Cell Movement, pubmed-meshheading:15481136-Cells, Cultured, pubmed-meshheading:15481136-Chemokine CX3CL1, pubmed-meshheading:15481136-Chemokines, CX3C, pubmed-meshheading:15481136-Endothelium, Vascular, pubmed-meshheading:15481136-Humans, pubmed-meshheading:15481136-Inflammation, pubmed-meshheading:15481136-Interferon-gamma, pubmed-meshheading:15481136-Membrane Proteins, pubmed-meshheading:15481136-Monocytes, pubmed-meshheading:15481136-Receptors, CCR2, pubmed-meshheading:15481136-Receptors, Chemokine, pubmed-meshheading:15481136-Receptors, IgG, pubmed-meshheading:15481136-Tumor Necrosis Factor-alpha, pubmed-meshheading:15481136-Umbilical Veins
pubmed:year
2004
pubmed:articleTitle
Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions.
pubmed:affiliation
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, JFB 816, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't