Phorbol ester-induced upregulation of polymorphonuclear leukocyte P-selectin ligand expression.
Proinflammatory stimuli cause the vascular endothelium to express P-selectin that tethers leukocytes by binding surface glycoprotein carbohydrate. While the activation of polymorphonuclear leukocytes (PMN) is associated with upregulation of the beta 2-integrins, there is little known about the regulated expression of the ligand for the endothelial P-selectin. We have used a soluble chimeric P-selectin protein as a probe for the expression of ligand on the surface of the PMN. Treatment with phorbol ester for more than 20 min stimulated P-selectin ligand expression. The upregulation of beta 2-integrin expression was affected in a similar manner. The mechanism of selectin ligand upregulation did not involve de novo protein synthesis, and may involve translocation of membranes containing performed intracellular ligand. C5a, which is generated in response to complement activation in vivo, also stimulated selectin ligand upregulation. Degranulation induced by nigericin increased ligand expression, and TNF-alpha treatment resulted in a modest upregulation.
Todderud
G
G
Bristol-Myers Squibb Pharmaceutical Research Institute, Buffalo, New York 14213-1091, USA.
Alford
J
J
Aruffo
A
A
Tramposch
K M
KM
D002478:Cells, Cultured; D006801:Humans; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D019007:P-Selectin / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D011993:Recombinant Fusion Proteins; D013755:Tetradecanoylphorbol Acetate