The prototype endothelial marker PAL-E is a leukocyte trafficking molecule.

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• The Pathologische Anatomie Leiden (PAL)-endothelium antibody, a long-standing marker for vascular endothelium, was recently identified to target plasmalemma vesicle-associated protein-1 (PV-1).
• The precise function of PV-1 within endothelial cells remained largely unknown despite its established use.

Purpose of the Study:

• To elucidate the functional role of plasmalemma vesicle-associated protein-1 (PV-1) in endothelial cells.
• To investigate the involvement of PV-1 in leukocyte transmigration.

Main Methods:

• Activation of human umbilical vein endothelial cells with tumor necrosis factor-alpha.
• In vitro transmigration assays using lymphocytes and endothelial cells.
• Immunofluorescence microscopy to visualize PV-1 and caveolin-1 distribution.
• Co-immunoprecipitation to assess PV-1 and vimentin association.
• In vivo studies using mouse models of acute peritonitis and air pouch inflammation.

Main Results:

• Tumor necrosis factor-alpha induced redistribution of PV-1 to the cell periphery.
• PV-1 and caveolin-1 formed rings around transmigrating lymphocytes in vitro.
• PV-1 was found to physically associate with vimentin.
• Anti-PV-1 antibody administration significantly inhibited lymphocyte transmigration in vitro and leukocyte migration in vivo, without affecting rolling or adhesion.

Conclusions:

• Leukocyte transendothelial migration is identified as the first characterized function of plasmalemma vesicle-associated protein-1 (PV-1).
• PV-1 plays a critical role in facilitating the passage of leukocytes across the endothelial barrier during inflammatory responses.