Neutrophil-neutrophil interactions under hydrodynamic shear stress involve L-selectin and PSGL-1: A mechanism that amplifies initial leukocyte accumulation on P-selectin in vitro

Bruce Walcheck, Kevin L. Moore, Rodger P. McEver, Takashi Kei Kishimoto

Research output: Contribution to journalArticlepeer-review

288 Scopus citations

Abstract

Leukocytes attach to and roll on inflamed endothelium and on leukocyte monolayers that form on the endothelial cells. Leukocyte-leukocyte interactions occurring under hydrodynamic shear stress are mediated by binding of L-selectin to unknown sialomucin-like glycoproteins. We show that purified neutrophil PSGL-1, a sialomucin glycoprotein that serves as a ligand for both P- and E-selectin, can also support the attachment and rolling of free flowing neutrophils in vitro. Neutrophil rolling on PSGL-1 was abolished by the anti-L-selectin mAb DREG200 and by the anti-PSGL-1 mAb PL1, indicating that L-selectin can interact directly with PSGL-1. Neutrophil rolling on neutrophil monolayers was also blocked by PL1 (60±9% SEM inhibition); however, DREG200 blocked more efficiently (93±7% SEM inhibition), suggesting that other L-selectin ligands may exist on the neutrophil surface. These studies demonstrate that PSGL-1 on the neutrophil surface is a major functional ligand for L-selectin. The avidity of this L-selectin-dependent adhesion event was sufficient to allow individual neutrophils rolling on P- selectin to capture free flowing neutrophils, which progressed to form linear strings and discrete foci of rolling neutrophils. Neutrophil accumulation on P-selectin accelerated with time as a result of neutrophil-assisted capture of free flowing neutrophils. When neutrophil-neutrophil interactions were blocked by DREG200, neutrophils accumulated on P-selectin in a random pattern and at a uniform rate. Thus, leukocyte-assisted capture of flowing leukocytes may play an important role in amplifying the rate of initial leukocyte recruitment at sites of inflammation.

Original languageEnglish (US)
Pages (from-to)1081-1087
Number of pages7
JournalJournal of Clinical Investigation
Volume98
Issue number5
DOIs
StatePublished - Sep 1 1996

Keywords

  • adhesion
  • glycoprotein
  • inflammation
  • mucin
  • myeloid cells
  • rolling

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