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 language | English |
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Pages (from-to) | 3576-3587 |
Number of pages | 12 |
Journal | The Journal of Immunology |
Volume | 198 |
Issue number | 9 |
DOIs | |
Publication status | Published - 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