TY - JOUR
T1 - P-selectin glycoprotein ligand-1-deficient mice have impaired leukocyte tethering to E-selectin under flow
AU - Xia, Lijun
AU - Sperandio, Markus
AU - Yago, Tadayuki
AU - Michael McDaniel, J.
AU - Cummings, Richard D.
AU - Pearson-White, Sonia
AU - Ley, Klaus
AU - McEver, Rodger P.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036218902&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036218902&partnerID=8YFLogxK
U2 - 10.1172/JCI0214151
DO - 10.1172/JCI0214151
M3 - Article
C2 - 11927621
AN - SCOPUS:0036218902
SN - 0021-9738
VL - 109
SP - 939
EP - 950
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 7
ER -