Overlapping functions of E- and P-selectin in neutrophil recruitment during acute inflammation.
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-P-selectin 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.
Homeister
J W
JW
Departments of Pathology and Internal Medicine and the Howard Hughes Medical Institute at The University of Michigan Medical Center, Ann Arbor, MI 48109-0680, USA.
Zhang
M
M
Frenette
P S
PS
Hynes
R O
RO
Wagner
D D
DD
Lowe
J B
JB
Marks
R M
RM
D000818:Animals; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D019040:E-Selectin / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D009195:Peroxidase / Q000032:analysis; D015054:Zymosan / Q000633:toxicity
D019040:E-Selectin; D019007:P-Selectin; D015054:Zymosan; D009195:Peroxidase