PSGL-1 derived from human neutrophils is a high-efficiency ligand for endothelium-expressed E-selectin under flow

Xiaoyan Zou, Vivek R.Shinde Patil, Nilesh M. Dagia, Lee A. Smith, Maureen J. Wargo, Kimberly A. Interliggi, Christopher M. Lloyd, David F.J. Tees, Bruce Walcheck, Michael B. Lawrence, Douglas J. Goetz

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

P-selectin glycoprotein ligand-1 (PSGL-1) has been proposed as an important tethering ligand for E-selectin and is expressed at a modest level on human leukocytes. Sialyl Lewis x (sLex)-like glycans bind to E-selectin and are expressed at a relatively high level on circulating leukocytes. It is unclear whether PSGL-1 has unique biochemical attributes that contribute to its role as an E-selectin ligand. To probe this issue, we conjugated microspheres with either sLex or PSGL-1 purified from myeloid cells (neutrophils and HL-60) and compared their adhesion to endothelial expressed E-selectin under defined shear conditions. We found that both sLex and PSGL-1 microspheres adhere to 4 h of IL-1β-activated human umbilical vein endothelial cells predominantly through E-selectin. Analysis of the adhesion revealed that the rate of initial tethering of the PSGL-1 microspheres to E-selectin was significantly greater than the rate of initial tethering of the sLex microspheres despite the fact that the sLex microspheres tested had higher ligand densities than the PSGL-1 microspheres. We also found that pretreatment of the PSGL-1 or sLex microspheres with HECA-452 had no significant effect on initial tethering to E-selectin. These results support the hypotheses that 1) PSGL-1 is a high-efficiency tethering ligand for E-selectin, 2) ligand biochemistry can significantly influence initial tethering to E-selectin, and 3) PSGL-1 tethering to E-selectin can occur via non-HECA-452 reactive epitopes.

Original languageEnglish (US)
Pages (from-to)C415-C424
JournalAmerican Journal of Physiology - Cell Physiology
Volume289
Issue number2 58-2
DOIs
StatePublished - Aug 2005

Keywords

  • Adhesion
  • Inflammation
  • Leukocyte

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