Linked Life Data

8943958

Source:http://linkedlifedata.com/resource/pubmed/id/8943958

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1997-1-2
pubmed:abstractText
Leukocyte capture and rolling are mediated by calcium-dependent lectins expressed on most leukocytes (L-selectin) and the vascular endothelium (P- and E-selectin). To study the role of the selectins during inflammation, we have investigated leukocyte rolling in venules of tumor necrosis factor-alpha (TNF-alpha)-treated mouse cremaster muscles in wild-type mice and gene-targeted mice with homozygous deficiency for L-, P-, or E-selectin (L-/-, P-/-, or E-/-, respectively). TNF-alpha treatment induces expression of E-selectin and increases expression of P-selectin on endothelial cells. Consistent with previous reports of redundant P- and E-selectin function, a combination of monoclonal antibodies (mAbs) against P- and E-selectin (RB40.34 and 9A9, respectively) was necessary to block rolling in wild-type mice. The rolling leukocyte flux fraction (percent rolling cells) in L-/- mice was similar to that in wild-type mice, but rolling in these mice was blocked by a P-selectin mAb. The velocity of rolling leukocytes in TNF-alpha-treated wild-type, P-/-, or L-/- mice was 5 to 10 times slower (3 to 7 microns/s) than during trauma-induced rolling (20 to 50 microns/s). In contrast, leukocytes in venules of TNF-alpha-treated E-/- mice rolled significantly faster (12 to 20 microns/s): the rolling leukocyte flux fraction was more than doubled compared with wild-type, L-/-, or P-/- mice; and the number of adherent leukocytes was reduced. Addition of an E-selectin mAb, but not a P-selectin mAb, increased rolling flux fraction and rolling velocity in wild-type mice. Histological analysis revealed that 90% to 95% of all leukocytes interacting (rolling and adherent) with the venular endothelium in TNF-alpha-treated wild-type, L-/-, P-/-, and E-/- mice were granulocytes. These results identify a previously unrecognized phenotype of E-/- mice by establishing that at the site densities prevailing in vivo, E-selectin in responsible for slow (approximately 5 microns/s) granulocyte rolling. E-selectin-dependent slow rolling drastically increases the transit time of leukocytes rolling through an inflamed tissue and thus aids in targeting leukocytes activated by chemoattractants to the inflammatory microenvironment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0009-7330
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1196-204
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Distinct phenotype of E-selectin-deficient mice. E-selectin is required for slow leukocyte rolling in vivo.
pubmed:affiliation
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville 22908, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.