CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

Transendothelial migration of leukocytes is a critical event for inflammation, but the molecular regulation of this event is only beginning to be understood. PECAM (CD31) is a major mediator of monocyte and neutrophil transmigration, and CD99 was recently defined as a second mediator of the transmig...

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Bibliographic Details
Published in:Journal of Immunology 2007-01, Vol.178 (2), p.1136-1143
Main Authors: Lou, Olivia, Alcaide, Pilar, Luscinskas, Francis W, Muller, William A
Format: Article
Language:English
Subjects:
12E7 Antigen
Antibodies - immunology
Antigens, CD - immunology
Antigens, CD - metabolism
Cell Adhesion
Cell Adhesion Molecules - immunology
Cell Adhesion Molecules - metabolism
Cell Communication
Cell Movement
Cell Separation
Cells, Cultured
Cytokines - metabolism
Endothelial Cells - cytology
Endothelial Cells - metabolism
Humans
Neutrophils - cytology
Neutrophils - metabolism
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Summary:Transendothelial migration of leukocytes is a critical event for inflammation, but the molecular regulation of this event is only beginning to be understood. PECAM (CD31) is a major mediator of monocyte and neutrophil transmigration, and CD99 was recently defined as a second mediator of the transmigration of monocytes. Expression of CD99 on the surface of circulating polymorphonuclear cells (PMN) is low compared with expression of CD99 on monocytes or expression of PECAM on PMN. We demonstrate here that, despite low expression of CD99, Fab of Abs against CD99 blocked over 80% of human neutrophils from transmigrating across HUVEC monolayers in an in vitro model of inflammation. Blocking CD99 on either the neutrophil or endothelial cell side resulted in a quantitatively equivalent block, suggesting a homophilic interaction between CD99 on the neutrophil and CD99 on the endothelial cell. Blocking CD99 and PECAM together resulted in additive effects, suggesting the two molecules work at distinct steps. Confocal microscopy confirmed that CD99-blocked neutrophils lodged in endothelial cell junctions at locations distal to PECAM-blocked neutrophils. The CD99-blocked PMN exhibited dynamic lateral movement within endothelial cell junctions, indicating that only the diapedesis step was blocked by interference with CD99. Anti-CD99 mAb also blocked PMN transmigration in a second in vitro model that incorporated shear stress. Taken together, the evidence demonstrates that PECAM and CD99 regulate distinct, sequential steps in the transendothelial migration of neutrophils during inflammation.
ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.178.2.1136