P-selectin glycoprotein ligand-1 supports rolling on E- and P-selectin in vivo

Abstract

Selectin-dependent rolling is the earliest observable event in the recruitment of leukocytes to inflamed tissues. Several glycoproteins decorated with sialic acid, fucose, and/or sulfate have been shown to bind the selectins. The best-characterized selectin ligand is P-selectin glycoprotein-1 (PSGL-1) that supports P-selectin– dependent rolling in vitro and in vivo. In vitro studies have suggested that PSGL-1 may also be a ligand for E- and L-selectins. To study the in vivo function of PSGL-1, without the influence of other leukocyte proteins, the authors observed the interaction of PSGL-1–coated microspheres in mouse venules stimulated to express P- and/or E-selectin. Microspheres coated with functional recombinant PSGL-1 rolled in surgically stimulated and tumor necrosis factor alpha (TNFα)-stimulated mouse venules. P-selectin deficiency or inhibition abolished microsphere rolling in surgically and TNFα-stimulated venules, whereas E-selectin deficiency or inhibition increased microsphere rolling velocity in TNFα-stimulated venules. The results suggest that P-selectin–PSGL-1 interaction alone is sufficient to mediate rolling in vivo and that E-selectin–PSGL-1 interaction supports slow rolling.

P‐Selectin and CD63 Use Different Mechanisms for Delivery to Weibel–Palade Bodies

“…Equivalent effects were seen in mocha mice (not shown). These responses are consistent with previously published studies (25–28). Haemodynamic parameters were similar to published values and were not substantially altered by antibody treatment.…”

“…Wild‐type C57 BL6 (WT) pearl and mocha mice (kind gift of M. S. Robinson) were prepared for intravital microscopy of the cremaster muscle as described (25,28). Briefly, mice were anaesthetized with a mixture of ketamine, xylazine and atropine, cannulations of the trachea, jugular vein and carotid artery were performed, and the cremaster muscle exposed and spread over a specialized viewing platform.…”

P‐Selectin Glycoprotein Ligand‐1 (rPSGL‐Ig)‐Mediated Blockade of CD62 Selectin Molecules Protects Rat Steatotic Liver Grafts from Ischemia/Reperfusion Injury

“…Although PSGL‐1 interacts with all three selectins (16,17), rPSGL‐Ig demonstrates the highest affinity for P‐, followed by E‐selectin, with L‐selectin displaying the lowest affinity for this recombinant protein (50). As a consequence, P‐selectin–PSGL−1 interaction alone is sufficient to mediate rolling in vivo , consistent with an observed defect in P‐selectin‐mediated but not E‐selectin‐mediated leukocyte rolling in PSGL‐1‐deficient mice (51).…”

P-selectin glycoprotein ligand-1–deficient mice have impaired leukocyte tethering to E-selectin under flow

“…Recombinant murine TNF-α (500 ng per mouse; R&D Systems Inc.) was diluted in 0.3 ml sterile saline and injected intrascrotally 2 hours before the beginning of each experiment. Microvessel diameters, lengths, and rolling leukocyte velocities were measured using a digital image processing system (30). Each rolling leukocyte passing a line perpendicular to the vessel axis was counted, and leukocyte rolling flux was expressed as leukocytes per minute.…”