G-CSF induces E-selectin ligand expression on human myeloid cells

Area of Science:

• Immunology
• Hematology
• Molecular Biology

Background:

• Clinical use of G-CSF is linked to vascular and inflammatory complications.
• The molecular mechanisms underlying these complications require further investigation.

Purpose of the Study:

• To investigate the molecular basis of G-CSF-induced vascular and inflammatory complications.
• To analyze the adherence of G-CSF-mobilized leukocytes to inflamed endothelium.

Main Methods:

• Parallel plate assays under physiologic flow conditions.
• Intravital microscopy in a mouse inflammation model.
• Biochemical studies, enzymatic treatments, and binding assays.

Main Results:

• G-CSF-mobilized leukocytes exhibit heightened adhesion to inflamed endothelium compared to unmobilized leukocytes.
• This increased adhesion is mediated by enhanced E-selectin receptor-ligand interactions.
• ML express potent E-selectin ligands, including HCELL and a novel ~65-kDa ligand, with increased glycosyltransferase transcripts.

Conclusions:

• G-CSF induces the expression of E-selectin ligands on myeloid cells.
• These findings provide mechanistic insight into G-CSF-related pathobiology and complications.
• HCELL and the novel ~65-kDa ligand are key contributors to G-CSF-induced myeloid cell adhesion.