tyrosine sulfation of native mouse psgl-1 is required for optimal leukocyte rolling on p-selectin in vivo酪氨酸硫酸盐化作用所需的本地鼠标psgl-1最佳p-selectin体内白细胞滚动.pdf

Tyrosine Sulfation of Native Mouse Psgl-1 Is Required for Optimal Leukocyte Rolling on P-Selectin In Vivo 1 1 1,2,3,4 Andrew D. Westmuckett *, Kelly M. Thacker , Kevin L. Moore 1 Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America, 2 Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America, 3 Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America, 4 Oklahoma Center of Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America Abstract Background: We recently demonstrated that tyrosine sulfation is an important contributor to monocyte recruitment and retention in a mouse model of atherosclerosis. P-selectin glycoprotein ligand-1 (Psgl-1) is tyrosine-sulfated in mouse monocyte/macrophages and its interaction with P-selectin is important in monocyte recruitment in atherosclerosis. However, whether tyrosine sulfation is required for the P-selectin binding function of mouse Psgl-1 is unknown. Here we test the function of native Psgl-1 expressed in leukocytes lacking endogenous tyrosylprotein sulfotransferase (TPST) activity. Methodology/Principal Findings: Psgl-1 function was assessed by examining P-selectin dependent leukocyte rolling in post-capillary venules of C57BL6 mice transplanted with hematopoietic progenitors from wild type (WTRB6) or Tpst1;Tpst2 double knockout mice (Tpst DKORB6) which lack TPST activity. We observed that rolling flux fractions were lower and leukocyte rolling velocities were higher in