Neutrophils, monocytes, and dendritic cells express the same specialized form of PSGL-1 as do skin-homing memory T cells: cutaneous lymphocyte antigen.
Memory T cells in inflamed skin express the cutaneous lymphocyte-associated antigen (CLA), a glycosylated epitope defined by the mAb HECA-452. We previously reported that on T cells, CLA occurs almost exclusively on the protein backbone of P-selectin glycoprotein ligand-1 (PSGL-1). T cells exhibiting the CLA isoform of PSGL-1 can tether and roll on both E- and P-selectin, while T cells expressing PSGL-1 without the CLA epitope do not bind E-selectin, though they may bind P-selectin. We show here that circulating neutrophils and monocytes, and cultured blood dendritic cells, also express CLA almost entirely as an isoform of PSGL-1. These cells all tether and roll on both E- and P-selectin. A chimeric fusion protein incorporating the 19 N-terminal amino acids of mature PSGL-1 exhibited HECA-452 immunoreactivity and supported rolling of CHO cells expressing either E- or P-selectin. These findings indicate a site for the CLA modification within the distal tip of PSGL-1, previously shown to be critical for P-selectin binding and to mediate some, but not all, of the E-selectin binding of PSGL-1. We hypothesize that the types of circulating leukocytes discussed above all use CLA/PSGL-1 to tether and roll on E- and P-selectin along the vascular endothelium.
Kieffer
J D
JD
Harvard Skin Disease Research Center, Dept. of Dermatology, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Fuhlbrigge
R C
RC
Armerding
D
D
Robert
C
C
Ferenczi
K
K
Camphausen
R T
RT
Kupper
T S
TS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D016466:CHO Cells; D002469:Cell Separation; D002478:Cells, Cultured; D006224:Cricetinae; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D020033:Protein Isoforms / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology; D013314:Stress, Mechanical; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D010446:Peptide Fragments; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins