Distinct but overlapping roles of P- and L-selectin in lipopolysaccharide (LPS)-induced leukocyte-endothelial interactions in the rat mesenteric microcirculation

Kelly L. Davenpeck, Bruce S. Bochner

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2 Scopus citations

Abstract

LPS is a potent stimulus of leukocyte infiltration, but the adhesion-related mechanisms responsible for LPS-induced cell recruitment in vivo remain poorly characterized. The objective of this study was to compare the roles of P- and L-selectin in LPS-induced inflammation. Using a model of intravital microscopy, we found that superfusion of the rat mesentery with LPS (1 μg/ml) resulted in a significant increase (≈5-10 fold) in leukocyte rolling and adherence, which was maintained for at least 2 hr. Administration of a P-sel. blocking mAb (1 mg/kg) just prior to LPS superfusion inhibited early, but not later, leukocyte rolling, while inhibiting LPS-induced leukocyte adherence through out. Leukocyte Rolling (cells/min) Leukocyte Adhesion (cells/100 μm) Time (min) LPS+ Vehicle LPS+Anti- P-Sel. LPS+Anti- L-Sel. LPS+ Vehicle LPS+Anti- P-Sel. LPS+Anti- L-Sel. 0 16.3 ± 4.0 12.9 ± 2.4 6.8 ± 07*0.88 ± 0.3 1.1 ± 0.5 17 ± 0.6 30 61.1 ± 4.5 31.8 ± 6.9*18.8 ± 4.4*5.0 ± 0.6 1.4 ± 0.3*4.3 ± 1.2 60 109.6 ± 6.8 92.8 ± 17.8 29.3 ± 5.4*7.0 ± 1.6 2.0 ± 0.5*6.8 ± 0.9 90 155.3 ± 27.5 117.2 ± 23.8 27.3 ± 3.9*5.5 ± 0.9 2.0 ± 0.6*7.2 ± 0.8 120 168.3 ± 27.8 120.8 ± 31.3 21.5 ± 6.0*8.5 ± 1.9 2.2 ± 1.1*6.1 ± 1.5 (*p<0.05 vs. LPS+vehicle, n=6 for all groups) Pretreatment with a L-sel. blocking mAb (100 μg/rat), but not a non-blocking mAb, dramatically inhibited LPS-induced leukocyte rolling, but did not inhibit leukocyte adhesion. Fucoidin (5 mg/kg), which blocks both P- and L-sel. function, completely inhibited leukocyte rolling and adhesion at all time points. Together, these data suggest that both P- and L-sel. play a role in LPS-induced leukocyte rolling, but only P-sel. is necessary for LPS-induced leukocyte adhesion.

Original languageEnglish (US)
Pages (from-to)A102
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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