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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-9-17
pubmed:abstractText
During infection, chemokines sequestered on endothelium induce recruitment of circulating leukocytes into the tissue where they chemotax along chemokine gradients toward the afflicted site. The aim of this in vivo study was to determine whether a chemokine gradient was formed intravascularly and influenced intraluminal neutrophil crawling and transmigration. A chemokine gradient was induced by placing a macrophage inflammatory protein-2 (MIP-2)-containing (CXCL2) gel on the cremaster muscle of anesthetized wild-type mice or heparanase-overexpressing transgenic mice (hpa-tg) with truncated heparan sulfate (HS) side chains. Neutrophil-endothelial interactions were visualized by intravital microscopy and chemokine gradients detected by confocal microscopy. Localized extravascular chemokine release (MIP-2 gel) induced directed neutrophil crawling along a chemotactic gradient immobilized on the endothelium and accelerated their recruitment into the target tissue compared with homogeneous extravascular chemokine concentration (MIP-2 superfusion). Endothelial chemokine sequestration occurred exclusively in venules and was HS-dependent, and neutrophils in hpa-tg mice exhibited random crawling. Despite similar numbers of adherent neutrophils in hpa-tg and wild-type mice, the altered crawling in hpa-tg mice was translated into decreased number of emigrated neutrophils and ultimately decreased the ability to clear bacterial infections. In conclusion, an intravascular chemokine gradient sequestered by endothelial HS effectively directs crawling leukocytes toward transmigration loci close to the infection site.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1924-31
pubmed:dateRevised
2011-10-6
pubmed:meshHeading
pubmed-meshheading:20530797-Animals, pubmed-meshheading:20530797-Cell Movement, pubmed-meshheading:20530797-Chemokine CXCL2, pubmed-meshheading:20530797-Chemotaxis, Leukocyte, pubmed-meshheading:20530797-Endothelium, Vascular, pubmed-meshheading:20530797-Glucuronidase, pubmed-meshheading:20530797-Green Fluorescent Proteins, pubmed-meshheading:20530797-Heparitin Sulfate, pubmed-meshheading:20530797-Leukocyte Rolling, pubmed-meshheading:20530797-Mice, pubmed-meshheading:20530797-Mice, Inbred C57BL, pubmed-meshheading:20530797-Mice, Transgenic, pubmed-meshheading:20530797-Microscopy, Fluorescence, pubmed-meshheading:20530797-Microscopy, Video, pubmed-meshheading:20530797-Muscles, pubmed-meshheading:20530797-Neutrophils, pubmed-meshheading:20530797-Receptors, Chemokine, pubmed-meshheading:20530797-Staphylococcal Infections, pubmed-meshheading:20530797-Staphylococcus aureus
pubmed:year
2010
pubmed:articleTitle
A chemotactic gradient sequestered on endothelial heparan sulfate induces directional intraluminal crawling of neutrophils.
pubmed:affiliation
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural