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CD99 plays a major role in the migration of monocytes through endothelial junctions

Nature Immunology volume 3, pages 143–150 (2002)Cite this article

Abstract

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.

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Figure 1: Characterization of the hec2 antigen.
Figure 2: CD99 is recognized by hec2.
Figure 3: Anti-CD99 selectively blocks leukocyte transendothelial migration.
Figure 4: CD99 is required for transmigration across cytokine-activated endothelium.
Figure 5: Endothelial cells and monocytes use CD99 for transmigration.
Figure 6: Homophilic interactions drive CD99-dependent cell adhesion.
Figure 7: CD99 functions distal to PECAM-1 in transmigration.
Figure 8: Blocking CD99 arrests monocytes part way through the endothelial cell junction.

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Acknowledgements

We thank K. Najid for technical assistance. Supported by NIH grants R01 HL64774 and HL46849 (to W. A. M.) and F32 HL10311 (to A. R. S.) and the Charles H. Revson Foundation (Z. M.).

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  1. Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, 10021, NY, USA

    Alan R. Schenkel, Zahra Mamdouh, Xia Chen, Ronald M. Liebman & William A. Muller

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Correspondence to William A. Muller.

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Schenkel, A., Mamdouh, Z., Chen, X. et al. CD99 plays a major role in the migration of monocytes through endothelial junctions. Nat Immunol 3, 143–150 (2002). https://doi.org/10.1038/ni749

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