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J Immunol. 2017 May 1;198(9):3576-3587. doi: 10.4049/jimmunol.1601636. Epub 2017 Mar 22.

Cell-Specific Variation in E-Selectin Ligand Expression among Human Peripheral Blood Mononuclear Cells: Implications for Immunosurveillance and Pathobiology.

Silva M1,2,3,4, Fung RKF2,3,5, Donnelly CB2,3,4, Videira PA1,6, Sackstein R7,3,4.

Author information

1
Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal.
2
Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02115.
3
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
4
Program of Excellence in Glycosciences, Harvard Medical School, Boston, MA 02115.
5
Medical Training and Administration Unit, Royal Prince Alfred Hospital, Sydney, New South Wales 2050, Australia; and.
6
Unidade de Ciências Biomoleculares Aplicadas, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
7
Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02115; rsackstein@partners.org.

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 and Western 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 α(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.

PMID:
28330896
PMCID:
PMC5426364
DOI:
10.4049/jimmunol.1601636
[Indexed for MEDLINE]
Free PMC Article

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