TY - JOUR
T1 - Overlapping functions of E- and P-selectin in neutrophil recruitment during acute inflammation
AU - Homeister, Jonathon W.
AU - Zhang, Mengkun
AU - Frenette, Paul S.
AU - Hynes, Richard O.
AU - Wagner, Denisa D.
AU - Lowe, John B.
AU - Marks, Rory M.
PY - 1998/10/1
Y1 - 1998/10/1
N2 - Selectin adhesion molecules mediate leukocyte rolling on activated endothelium, a prerequisite to leukocyte accumulation at sites of inflammation. The precise role of each selectin (E-, P-, and L-) in this process is unclear and may vary depending on the particular inflammatory stimulus, vascular bed, leukocyte subset, and species; most data suggest discrete functional roles for each selectin. To define the relative roles of E- and P-selectin in mediating neutrophil accumulation in acute dermal inflammation, mice genetically deficient in E-selectin, P-selectin, or both E- and P-selectin were injected intradermally with zymosan. Luminal endothelial expression of E- and P-selectin in response to zymosan was documented in wild-type mice by intravenous administration of fluorochrome- labeled anti-E- and anti-Pselectin antibodies. In mice deficient in E- or P- selectin, neutrophil accumulation was unchanged or only subtly reduced relative to wild-type control mice. In mice deficient in both E- and P- selectin, neutrophil accumulation was significantly reduced (87% at 4 hours and 79% at 8 hours). These data demonstrate that, in this model of acute inflammation, there is considerable overlap in the functions of E- and P- selectin; loss of both selectins was required to impair neutrophil accumulation.
AB - Selectin adhesion molecules mediate leukocyte rolling on activated endothelium, a prerequisite to leukocyte accumulation at sites of inflammation. The precise role of each selectin (E-, P-, and L-) in this process is unclear and may vary depending on the particular inflammatory stimulus, vascular bed, leukocyte subset, and species; most data suggest discrete functional roles for each selectin. To define the relative roles of E- and P-selectin in mediating neutrophil accumulation in acute dermal inflammation, mice genetically deficient in E-selectin, P-selectin, or both E- and P-selectin were injected intradermally with zymosan. Luminal endothelial expression of E- and P-selectin in response to zymosan was documented in wild-type mice by intravenous administration of fluorochrome- labeled anti-E- and anti-Pselectin antibodies. In mice deficient in E- or P- selectin, neutrophil accumulation was unchanged or only subtly reduced relative to wild-type control mice. In mice deficient in both E- and P- selectin, neutrophil accumulation was significantly reduced (87% at 4 hours and 79% at 8 hours). These data demonstrate that, in this model of acute inflammation, there is considerable overlap in the functions of E- and P- selectin; loss of both selectins was required to impair neutrophil accumulation.
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U2 - 10.1182/blood.v92.7.2345
DO - 10.1182/blood.v92.7.2345
M3 - Article
C2 - 9746773
AN - SCOPUS:0032189827
SN - 0006-4971
VL - 92
SP - 2345
EP - 2352
JO - Blood
JF - Blood
IS - 7
ER -