Neutrophil platelet endothelial cell adhesion molecule-1 participates in neutrophil recruitment at inflammatory sites and is down-regulated after leukocyte extravasation.
Platelet endothelial cell adhesion molecule-1 (PECAM-1), a member of the Ig superfamily, is found on endothelial cells and neutrophils, and has been shown to be involved in the migration of leukocytes across the endothelium. Although studies have supported a role for endothelial PECAM-1 in this process, the participation of neutrophil PECAM-1 in vivo has not been unambiguously demonstrated. Therefore, to examine the involvement of neutrophil PECAM-1 in leukocyte recruitment, we studied the effect of a blocking Ab against murine PECAM-1 on neutrophil recruitment in an established model of murine peritonitis and in a murine model for studying leukocyte-endothelial interactions involving the human vasculature. These studies not only confirmed that neutrophil PECAM-1 is important in the accumulation of neutrophils at inflammatory sites, but that extravasated neutrophils displayed decreased surface expression of PECAM-1. In vitro, the surface expression of murine neutrophil PECAM-1 was not decreased significantly by inflammatory mediators, but was reduced after transendothelial migration. These studies, consistent with previous in vitro observations, confirm that neutrophil PECAM-1, as well as endothelial PECAM-1, is involved in the recruitment of neutrophils into inflammatory sites in vivo, and suggest that the expression of neutrophil PECAM-1 is down-regulated after extravasation into inflamed tissues possibly as a result of engagement of its ligand.
Christofidou-Solomidou
M
M
Pulmonary and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Nakada
M T
MT
Williams
J
J
Muller
W A
WA
DeLisser
H M
HM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009504:Neutrophils / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha