Cell-Specific Variation in E-Selectin ligand expression among human peripheral blood mononuclear cells: Implications for immunosurveillance and pathobiology

M. Silva, R.K.F. Fung, C.B. Donnelly, P.A. Videira, R. Sackstein

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Both host defense and immunopathology are shaped by the ordered recruitment of circulating leukocytes to affected sites, a process initiated by binding of blood-borne cells to E-selectin displayed at target endothelial beds. Accordingly, knowledge of the expression and function of leukocyte E-selectin ligands is key to understanding the tempo and specificity of immunoreactivity. In this study, we performed E-selectin adherence assays under hemodynamic flow conditions coupled with flow cytometry andWestern blot analysis to elucidate the function and structural biology of glycoprotein E-selectin ligands expressed on human PBMCs. Circulating monocytes uniformly express high levels of the canonical E-selectin binding determinant sialyl Lewis X (sLeX) and display markedly greater adhesive interactions with E-selectin than do circulating lymphocytes, which exhibit variable E-selectin binding among CD4+ and CD8+ T cells but no binding by B cells. Monocytes prominently present sLeX decorations on an array of protein scaffolds, including P-selectin glycoprotein ligand-1, CD43, and CD44 (rendering the E-selectin ligands cutaneous lymphocyte Ag, CD43E, and hematopoietic cell E-selectin/L-selectin ligand, respectively), and B cells altogether lack E-selectin ligands. Quantitative PCR gene expression studies of glycosyltransferases that regulate display of sLeX reveal high transcript levels among circulating monocytes and low levels among circulating B cells, and, commensurately, cell surface a(1,3)-fucosylation reveals that acceptor sialyllactosaminyl glycans convertible into sLeX are abundantly expressed on human monocytes yet are relatively deficient on B cells. Collectively, these findings unveil distinct cell-specific patterns of E-selectin ligand expression among human PBMCs, indicating that circulating monocytes are specialized to engage E-selectin and providing key insights into the molecular effectors mediating recruitment of these cells at inflammatory sites. Copyright © 2017 by The American Association of Immunologists, Inc.
Original languageEnglish
Pages (from-to)3576-3587
Number of pages12
JournalJournal of Immunology
Volume198
Issue number9
DOIs
Publication statusPublished - 1 May 2017

Keywords

  • 5-acetylneuraminyl-(2-3)-galactosyl-(1-4)-(fucopyranosyl-(1-3))-N-acetylglucosamine
  • endothelial leukocyte adhesion molecule 1
  • glycosyltransferase
  • Hermes antigen
  • leukosialin
  • ligand
  • oligosaccharide
  • prostaglandin F
  • prostaglandin F1
  • SELE protein, human
  • antibody specificity
  • cell adhesion
  • endothelium cell
  • gene expression regulation
  • human
  • immunology
  • immunosurveillance
  • metabolism
  • mononuclear cell
  • physiology
  • umbilical vein endothelial cell
  • Antigens, CD43
  • Antigens, CD44
  • Cell Adhesion
  • E-Selectin
  • Endothelial Cells
  • Gene Expression Regulation
  • Glycosyltransferases
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Immunologic Surveillance
  • Leukocytes, Mononuclear
  • Ligands
  • Oligosaccharides
  • Organ Specificity
  • Prostaglandins F

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