Physiological and pathological functions of PSGL1selectin interactions

The contributions of PSGL-1 to leukocyte adhesion in vivo have been documented in numerous studies, mostly in murine models. Studies with blocking mAbs to the N-terminal region of PSGL-1 initially demonstrated that PSGL-1 is the dominant ligand for mediating leukocyte rolling on P-selectin on inflamed endothelial cells in vivo 108, 109 (Fig. 2). Targeted disruption of the gene encoding murine PSGL-1 confirmed these observations very few PSGL-1-deficient leukocytes roll on P-selectin on...

Role of Lselectin in disease

Aberrant leukocyte recruitment, either in location or duration, is a major hallmark of inflammatory disease. As such, identification of the molecular pathways involved in mediating this recruitment has received a great deal of attention. An accumulating body of evidence, from both human patients and animal models, shows L-selec-tin to be a key regulator of leukocyte migration in a number of disease conditions. Therefore, selective targeting of L-selectin function may be of therapeutic benefit...

Structure and expression

L-selectin (CD62L) belongs to the selectin family of adhesion molecules that also contains two other structurally related members, E- and P-selectin (CD62E and CD62P, respectively, see the chapter by D. C. Bullard). The selectins share a unique extracellular domain organization composed of an N-terminal calcium-dependent lectin domain, an epidermal growth factor (EGF)-like domain, and short consensus repeat (SCR) units homologous to domains found in complement regulatory proteins (Fig. 1). The...

Structure and tissue distribution of PSGL1

PSGL-1 was initially described as the dominant glycoprotein ligand for P-selectin on human myeloid cells 6 . Biochemical characterization indicated that PSGL-1 is a disulfide-linked homodimer with two 120-kDa subunits as determined by SDS-PAGE. Each subunit has two to three N-glycans that are dispensable for binding Adhesion Molecules Function and Inhibition, edited by Klaus Ley 2007 Birkh user Verlag Basel Switzerland to P-selectin. In contrast, it has many clustered, sialylated O-glycans that...

List of contributors

Auerbach, Center for Excellence in Vascular Biology, Departments of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA e-mail sauerbach rics.bwh.harvard.edu Daniel C. Bullard, Department of Genetics, Kaul Building 640A, 720 South 20th Street, University of Alabama at Birmingham, Birmingham, AL 35294, USA e-mail dcbullard genetics.uab.edu Stefan Butz, Max-Planck-Institute for Molecular Biomedicine, R ntgenstra e 20, 48149 M...