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

作者：Lijun Xia, Markus Sperandio, Tadayuki Yago, J. Michael McDaniel, Richard D. Cummings, Sonia H. Pearson-White, Klaus F. Ley, Rodger P. McEver · 发表于：Journal of Clinical Investigation · 年份：2002 · DOI：10.1172/jci0214151 · 被引用次数：198 · 研究领域：Cell Adhesion Molecules Research、Chemokine receptors and signaling、Protease and Inhibitor Mechanisms

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.