Linked Life Data

15518334

Source:http://linkedlifedata.com/resource/pubmed/id/15518334

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-11-2
pubmed:abstractText
Non-peptide antagonists of chemokine receptors are considered an intriguing alternative for the treatment of acute and chronic diseases. Particularly the recruitment of neutrophils to inflammatory sites often causes harmful side effects and is mediated by chemokine ligands of the CXC chemokine receptor 2 (CXCR2). Hence, this receptor has been proposed as an important target for novel drugs. This study investigates the potential of the non-peptide CXCR2 antagonist SB 455821 to block neutrophil migration in mice. By using bone marrow derived neutrophils we established a migration assay which revealed SB 455821 as a potent inhibitor of macrophage inflammatory protein 2 (MIP-2)-induced neutrophil migration in vitro (IC50-20 nM). In vivo, injection of MIP-2 into the peritoneal cavities of mice markedly increased neutrophil numbers in peritoneal lavages which were reduced to control levels by co-administration of SB 455821 indicating that the compound effectively binds to the receptor under physiological conditions and exhibits biological activity in vivo. Nevertheless, using intraperitoneal injection of zymosan as a complex inflammatory stimulus, SB 455821 was unable to block neutrophil recruitment to the peritoneal cavity of mice possibly due to other chemotactic mediators overruling signals derived from CXCR2 ligands. Our data show that SB 455821 blocks MIP-2-induced neutrophil migration in vitro and after injection in mice suggesting that selective CXCR2 antagonists may be useful drugs in diseases where neutrophil accumulation plays a major role and leads to exacerbation of acute or chronic inflammations.
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
225-33
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
A synthetic, non-peptide CXCR2 antagonist blocks MIP-2-induced neutrophil migration in mice.
pubmed:affiliation
Institute for Clinical Microbiology, Immunology and Hygiene, University of Erlangen, Wasserturmstrasse 3, Erlangen 91054, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't