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 1

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Strategy for disrupting the murine PSGL-1 gene. (a) Partial restriction ...
Strategy for disrupting the murine PSGL-1 gene. (a) Partial restriction map of the murine PSGL-1 gene. The three restriction fragments used for construction of the targeting vector are shown at the top. (b) Diagram of the targeting vector. (c) Diagram of the targeted gene, the probes used for Southern blotting, and the predicted sizes of the restriction fragments for the WT and targeted alleles. (d) Southern blots of genomic DNA from targeted and WT ES cells. (e) Southern blots of genomic DNA isolated from tails of PSGL-1+/+, PSGL-1+/–, and PSGL-1–/– mice.