Linked Life Data

11086073

Source:http://linkedlifedata.com/resource/pubmed/id/11086073

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2000-12-7
pubmed:abstractText
CCR5 and CXC chemokine receptor 4 (CXCR4) are coreceptors for CD4 as defined by HIV-1 glycoprotein (gp) 120 binding. Pretreatment of T cells with gp120 results in modulation of both CCR5 and CXCR4 responsiveness, which is dependent upon p56(lck) enzymatic activity. The recent findings that pretreatment of T cells with a natural CD4 ligand, IL-16, could alter cellular responsiveness to macrophage-inflammatory protein-1ss (MIP-1ss) stimulation, prompted us to investigate whether IL-16 could also alter CXCR4 signaling. These studies demonstrate that IL-16/CD4 signaling in T lymphocytes also results in loss of stromal derived factor-1alpha (SDF-1alpha)/CXCR4-induced chemotaxis; however, unlike MIP-1ss/CCR5, the effects were not reciprocal. There was no effect on eotaxin/CCR3-induced chemotaxis. Desensitization of CXCR4 by IL-16 required at least 10-15 min pretreatment; no modulation of CXCR4 expression was observed, nor was SDF-1alpha binding altered. Using murine T cell hybridomas transfected to express native or mutated forms of CD4, it was determined that IL-16/CD4 induces a p56(lck)-dependent inhibitory signal for CXCR4, which is independent of its tyrosine catalytic activity. By contrast, IL-16/CD4 desensitization of MIP-1ss/CCR5 responses requires p56(lck) enzymatic activity. IL-16/CD4 inhibition of SDF-1alpha/CXCR4 signals requires the presence of the Src homology 3 domain of p56(lck) and most likely involves activation of phosphatidylinositol-3 kinase. These studies indicate the mechanism of CXCR4 receptor desensitization induced by a natural ligand for CD4, IL-16, is distinct from the inhibitory effects induced by either gp120 or IL-16 on CCR5.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6356-63
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11086073-Animals, pubmed-meshheading:11086073-Antigens, CD4, pubmed-meshheading:11086073-Cell Line, pubmed-meshheading:11086073-Cell Migration Inhibition, pubmed-meshheading:11086073-Chemokine CXCL12, pubmed-meshheading:11086073-Chemokines, CXC, pubmed-meshheading:11086073-Chemotaxis, Leukocyte, pubmed-meshheading:11086073-Enzyme Activation, pubmed-meshheading:11086073-Humans, pubmed-meshheading:11086073-Hybridomas, pubmed-meshheading:11086073-Interleukin-16, pubmed-meshheading:11086073-Lymphocyte Specific Protein Tyrosine Kinase p56(lck), pubmed-meshheading:11086073-Mice, pubmed-meshheading:11086073-Receptors, CXCR4, pubmed-meshheading:11086073-Stromal Cells, pubmed-meshheading:11086073-T-Lymphocytes, pubmed-meshheading:11086073-Time Factors, pubmed-meshheading:11086073-src Homology Domains
pubmed:year
2000
pubmed:articleTitle
Desensitization of CXC chemokine receptor 4, mediated by IL-16/CD4, is independent of p56lck enzymatic activity.
pubmed:affiliation
Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't