Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice.
P selectin, expressed on surfaces of activated endothelial cells and platelets, is an adhesion receptor for leukocytes. We report that P selectin-deficient mice, generated by gene targeting in embryonic stem cells, exhibit a number of defects in leukocyte behavior, including elevated numbers of circulating neutrophils, virtually total absence of leukocyte rolling in mesenteric venules, and delayed recruitment of neutrophils to the peritoneal cavity upon experimentally induced inflammation. These results clearly demonstrate a role for P selectin in leukocyte interactions with the vessel wall and in the early steps of leukocyte recruitment at sites of inflammation. These mutant mice should prove useful in deciphering the contributions of P selectin in various inflammatory responses as well as in platelet functions.
Mayadas
T N
TN
New England Medical Center, Department of Medicine, Boston, Massachusetts.
Johnson
R C
RC
Rayburn
H
H
Hynes
R O
RO
Wagner
D D
DD
D000483:Alleles; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002678:Chimera; D019040:E-Selectin; D004622:Embryo, Mammalian; D004727:Endothelium / Q000378:metabolism; D005434:Flow Cytometry; D005838:Genotype; D007962:Leukocytes / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000502:physiology; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D013234:Stem Cells / Q000502:physiology; D014158:Transcription, Genetic
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D012313:RNA