P-selectin glycoprotein ligand-1–deficient mice have impaired leukocyte tethering to E-selectin under flow
Lijun Xia, … , Klaus Ley, Rodger P. McEver
Lijun Xia, … , Klaus Ley, Rodger P. McEver
Published April 1, 2002
Citation Information: J Clin Invest. 2002;109(7):939-950. https://doi.org/10.1172/JCI14151.
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Article Immunology

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

Abstract

P-selectin glycoprotein ligand-1 (PSGL-1) mediates rolling of leukocytes on P-selectin under flow. The glycoproteins that enable leukocyte tethering to or rolling on E-selectin are not known. We used gene targeting to prepare PSGL-1–deficient (PSGL-1–/–) mice, which were healthy but had moderately elevated total blood leukocytes. Fluid-phase E-selectin bound to approximately 70% fewer sites on PSGL-1–/– than PSGL-1+/+ neutrophils. Compared with PSGL-1+/+ leukocytes, significantly fewer PSGL-1–/– leukocytes rolled on E-selectin in vitro, because their initial tethering to E-selectin was impaired. The residual cells that tethered rolled with the same shear resistance and velocities as PSGL-1+/+ leukocytes. Compared with PSGL-1+/+ mice, significantly fewer PSGL-1–/– leukocytes rolled on E-selectin in TNF-α–treated venules of cremaster muscle in which P-selectin function was blocked by an mAb. The residual PSGL-1–/– leukocytes that tethered rolled with slow velocities equivalent to those of PSGL-1+/+ leukocytes. These results reveal a novel function for PSGL-1 in tethering leukocytes to E-selectin under flow.

Authors

Lijun Xia, Markus Sperandio, Tadayuki Yago, J. Michael McDaniel, Richard D. Cummings, Sonia Pearson-White, Klaus Ley, Rodger P. McEver

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Figure 5

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Rolling of PSGL-1+/+ and PSGL-1–/– leukocytes on P-selectin in vitro. (a...
Rolling of PSGL-1+/+ and PSGL-1–/– leukocytes on P-selectin in vitro. (a) Peripheral blood leukocytes were perfused over P-selectin–IgM captured on adsorbed mAb against the Fc portion of human IgM or over adsorbed mAb alone, in the presence or absence of EDTA or anti–P-selectin mAb RB40.34. After 5 minutes, the number of rolling cells was quantified. (b) Leukocytes were perfused over a very high density of P-selectin–IgM at the indicated wall shear stress in the presence or absence of anti–PSGL-1 mAb 4RA10 and/or anti–P-selectin mAb RB40.34. After 5 minutes, the number of rolling cells was quantified. (c and d) Leukocytes were allowed to accumulate on P-selectin at 0.5 dyn/cm2. Wall shear stress was increased every 30 seconds, and the percentage of cells remaining adherent and the rolling velocities of the cells were determined. (e) PSGL-1–/– leukocytes preincubated with or without Pronase, OSGE, or anti-CD24 mAb 79 or M1.69 were perfused over high density P-selectin in the presence or absence of anti–P-selectin mAb RB40.34. After 5 minutes, the number of rolling cells was quantified. The data in each panel represent the mean ± SEM of three or four experiments.*P < 0.05 vs. untreated PSGL-1–/–.