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 β2-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 β2-integrin expression was affected in a similar manner. The mechanism of selectin ligand upregulation did not involvede novoprotein synthesis, and may involve translocation of membranes containing preformed intracellular ligand. C5a, which is generated in response to complement activationin vivo,also stimulated selectin ligand upregulation. Degranulation induced by nigericin increased ligand expression, and TNF-α treatment resulted in a modest upregulation.