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

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

Research output: Contribution to journalArticlepeer-review

391 Scopus citations


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 I (PECAM-I, also known as CD31), another adhesion molecule involved in transmigration, played its critical role. Confocal microscopy showed that anti-PECAM-I 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-I and CD99.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalNature Immunology
Issue number2
StatePublished - 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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