The prototype endothelial marker PAL-E is a leukocyte trafficking molecule.
Pathologische Anatomie Leiden-endothelium antibody has been used for more than 20 years as a marker for vascular endothelium. Despite its widespread use, the target of this antibody was only recently identified as plasmalemma vesicle-associated protein-1 (PV-1). However, no function has been identified for this molecule. Here we report that activation of human umbilical vein endothelial cells with tumor necrosis factor-alpha resulted in a remarkable redistribution of PV-1 toward the peripheral areas of the cells. Furthermore, in vitro endpoint transmigration experiments showed that transcellularly migrating lymphocytes are surrounded by rings containing PV-1 and caveolin-1. Moreover, PV-1 associates physically with vimentin. In addition, administration of anti-PV-1 antibody during capillary flow assays resulted in a significant inhibition of lymphocyte transmigration through the endothelial cell layer, whereas rolling and adhesion were unaffected. In vivo blockage of PV-1 by an antibody in acute peritonitis and air pouch model resulted in a significant decrease in the number of migrating leukocytes. Here we thus define leukocyte transendothelial migration as the first known function for PV-1.
MediCity Research Laboratory and Department of Medical Microbiology, University of Turku and National Public Health Institute, Turku, Finland.
Johannes
J
Keuschnigg
Tiina
T
Henttinen
Kaisa
K
Auvinen
Marika
M
Karikoski
Marko
M
Salmi
Sirpa
S
Jalkanen
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D042783:Endothelial Cells / Q000166:cytology*; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D014746:Vimentin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D002352:Carrier Proteins; D008565:Membrane Proteins; C486771:PLVAP protein, human; D014746:Vimentin