P- and L-selectin mediate distinct but overlapping functions in endotoxin-induced leukocyte-endothelial interactions in the rat mesenteric microcirculation.
Endotoxin is a potent stimulus of leukocyte infiltration, but the adhesion-related mechanisms responsible for LPS-induced cell recruitment events in vivo remain poorly characterized. Utilizing intravital microscopy, we examined the role of P- and L-selectin in LPS-induced inflammation. We demonstrated that superfusion of rat mesentery with LPS resulted in significant increases in both leukocyte rolling and adherence, which were maintained for at least 2 h. Pretreatment with a P-selectin neutralizing mAb only partially inhibited LPS-induced leukocyte rolling, but completely inhibited LPS-induced leukocyte adherence throughout the 2-h observation period. Pretreatment with an L-selectin neutralizing mAb dramatically inhibited LPS-induced increases in leukocyte rolling, but unlike the P-selectin mAb did not inhibit leukocyte adhesion. Fucoidin, which blocks both P- and L-selectin function, completely inhibited LPS-induced leukocyte rolling and adhesion. Consistent with previous studies, leukocyte rolling velocities on P-selectin were observed to be far less than velocities observed for leukocytes rolling on L-selectin in vivo. These data suggest that P-selectin plays a role in LPS-induced rolling and is essential for LPS-induced leukocyte adherence, while L-selectin functions in LPS-induced rolling, but not in adhesion.
Davenpeck
K L
KL
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Steeber
D A
DA
Tedder
T F
TF
Bochner
B S
BS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D019041:L-Selectin / Q000502:physiology*; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019007:P-Selectin / Q000502:physiology*; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D019007:P-Selectin; D011134:Polysaccharides; D019041:L-Selectin; C007789:fucoidan