Article abstract
Nature Chemical Biology 4, 751 - 757 (2008)
Published online: 19 October 2008 | doi:10.1038/nchembio.116
CD15 expression in human myeloid cell differentiation is regulated by sialidase activity
Samah Zeineb Gadhoum1,2 & Robert Sackstein1,2,3,4
Abstract
The glycan determinant CD15 (also known as Lewis x, or Lex) is a distinguishing marker for human myeloid cells and mediates neutrophil adhesion to dendritic cells. Despite broad interest in this structure, the mechanisms underlying CD15 expression remain relatively uncharacterized. Accordingly, we investigated the molecular basis of increasing CD15 expression associated with human myeloid cell differentiation. Flow cytometric analysis of differentiating cells together with biochemical studies using inhibitors of glycan synthesis and of sialidases showed that increased CD15 expression is not due to de novo biosynthesis of CD15, but results predominantly from induction of 
(2-3)-sialidase activity, which yields CD15 from cell-surface sialyl-CD15 (also known as sialyl-Lewis x, sLex or CD15s). This differentiation-associated conversion of surface CD15s to CD15 occurs mainly on glycoproteins. Until now, modulation of post-translational glycan modifications has been attributed solely to dynamic variations in glycosyltransferase expression. Our results unveil a new paradigm by demonstrating a critical role for post-Golgi membrane glycosidase activity in the 'biosynthesis' of a key glycan determinant.
- Department of Dermatology, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
- Harvard Skin Disease Research Center, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
- Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
- Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
Correspondence to: Robert Sackstein1,2,3,4 e-mail: rsackstein@rics.bwh.harvard.edu
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