CD99 plays a major role in the migration of monocytes through endothelial junctions.
CD99 is a heavily O-glycosylated 32-kD type I transmembrane protein that is expressed on most hematopoietic cells. We show here that CD99 is expressed on endothelial cells and is concentrated at the borders between confluent cells. We found that a monoclonal antibody to CD99, hec2, selectively inhibited diapedesis of monocytes across endothelial cells by >90%. Diapedesis involved the homophilic interaction of CD99 on monocytes with CD99 on endothelial junctions. CD99 functioned distally to the point at which platelet-endothelial cell adhesion molecule 1 (PECAM-1, also known as CD31), another adhesion molecule involved in transmigration, played its critical role. Confocal microscopy showed that anti-PECAM-1 arrested leukocytes on the apical surface of endothelium, whereas blocking CD99 arrested monocytes at a point where they were partially through the junction. Therefore, diapedesis, the forward migration of leukocytes through endothelial junctions, is regulated sequentially by two distinct molecules, PECAM-1 and CD99.
Schenkel
Alan R
AR
Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Mamdouh
Zahra
Z
Chen
Xia
X
Liebman
Ronald M
RM
Muller
William A
WA
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000302:isolation & purification*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000302:isolation & purification*; D002465:Cell Movement / Q000276:immunology*; D016764:Cell Polarity; D004730:Endothelium, Vascular / Q000276:immunology*; D006023:Glycoproteins / Q000302:isolation & purification; D006801:Humans; D007365:Intercellular Junctions / Q000737:chemistry*; D007375:Interleukin-1 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D007375:Interleukin-1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha