Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-11-3
pubmed:abstractText
We have previously shown that members of the ELR(+) CXC chemokine family, including IL-8; growth-related oncogenes alpha, beta, and gamma; granulocyte chemotactic protein 2; and epithelial neutrophil-activating protein-78, can mediate angiogenesis in the absence of preceding inflammation. To date, the receptor on endothelial cells responsible for chemotaxis and neovascularization mediated by these ELR(+) CXC chemokines has not been determined. Because all ELR(+) CXC chemokines bind to CXC chemokine receptor 2 (CXCR2), we hypothesized that CXCR2 is the putative receptor for ELR(+) CXC chemokine-mediated angiogenesis. To test this postulate, we first determined whether cultured human microvascular endothelial cells expressed CXCR2. CXCR2 was detected in human microvascular endothelial cells at the protein level by both Western blot analysis and immunohistochemistry using polyclonal Abs specific for human CXCR2. To determine whether CXCR2 played a functional role in angiogenesis, we determined whether this receptor was involved in endothelial cell chemotaxis. We found that microvascular endothelial cell chemotaxis in response to ELR(+) CXC chemokines was inhibited by anti-CXCR2 Abs. In addition, endothelial cell chemotaxis in response to ELR(+) CXC chemokines was sensitive to pertussis toxin, suggesting a role for G protein-linked receptor mechanisms in this biological response. The importance of CXCR2 in mediating ELR(+) CXC chemokine-induced angiogenesis in vivo was also demonstrated by the lack of angiogenic activity induced by ELR(+) CXC chemokines in the presence of neutralizing Abs to CXCR2 in the rat corneal micropocket assay, or in the corneas of CXCR2(-/-) mice. We thus conclude that CXCR2 is the receptor responsible for ELR(+) CXC chemokine-mediated angiogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5269-77
pubmed:dateRevised
2009-4-16
pubmed:meshHeading
pubmed-meshheading:11046061-Administration, Topical, pubmed-meshheading:11046061-Amino Acid Motifs, pubmed-meshheading:11046061-Amino Acid Sequence, pubmed-meshheading:11046061-Angiogenesis Inhibitors, pubmed-meshheading:11046061-Animals, pubmed-meshheading:11046061-Antibodies, Blocking, pubmed-meshheading:11046061-Cell Migration Inhibition, pubmed-meshheading:11046061-Cells, Cultured, pubmed-meshheading:11046061-Chemokines, CXC, pubmed-meshheading:11046061-Cornea, pubmed-meshheading:11046061-Endothelium, Vascular, pubmed-meshheading:11046061-Humans, pubmed-meshheading:11046061-Immune Sera, pubmed-meshheading:11046061-Mice, pubmed-meshheading:11046061-Mice, Inbred C57BL, pubmed-meshheading:11046061-Mice, Knockout, pubmed-meshheading:11046061-Microcirculation, pubmed-meshheading:11046061-Molecular Sequence Data, pubmed-meshheading:11046061-Neovascularization, Physiologic, pubmed-meshheading:11046061-Pertussis Toxin, pubmed-meshheading:11046061-Rats, pubmed-meshheading:11046061-Receptors, Interleukin-8B, pubmed-meshheading:11046061-Virulence Factors, Bordetella
pubmed:year
2000
pubmed:articleTitle
The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity.
pubmed:affiliation
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't