Glycobiology, 2002, Vol. 12, No. 10 613-622
© 2002 Oxford University Press
TNF-
increases the carbohydrate sulfation of CD44: induction of 6-sulfo N-acetyl lactosamine on N- and O-linked glycans
3 Department of Microbiology and Immunology, 6174 University Boulevard, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada, and 4 Program of Experimental Pathology, Aichi Cancer Center, Nagoya 464, Japan
CD44 and sulfation have both been implicated in leukocyte adhesion. In monocytes, the inflammatory cytokine tumor necrosis factor 
(TNF-) stimulates CD44 sulfation, and this correlates with the induction of CD44-mediated adhesion events. However, little is known about the sulfation of CD44 or its induction by inflammatory cytokines. We determined that TNF- induces the carbohydrate sulfation of CD44. CD44 was established as a major sulfated cell surface protein on myeloid cells. In the SR91 myeloid cell line, the majority of CD44 sulfation was attributed to the glycosaminoglycan chondroitin sulfate. However, TNF- stimulation increased CD44 sulfation two- to threefold, largely attributed to the increased sulfation of N- and O-linked glycans on CD44. Therefore, TNF- induced a decrease in the percentage of CD44 sulfation due to chondroitin sulfate and an increase due to N- and O-linked sulfation. Furthermore, TNF- induced the expression of 6-sulfo N-acetyl lactosamine (LacNAc)/Lewis x on these cells, which was detected by a monoclonal antibody after neuraminidase treatment. This 6-sulfo LacNAc/Lewis x epitope was induced on N-linked and (to a lesser extent) on O-linked glycans present on CD44. This demonstrates that CD44 is modified by sulfated carbohydrates in myeloid cells and that TNF- modifies both the type and amount of carbohydrate sulfation occurring on CD44. In addition, it demonstrates that TNF- can induce the expression of 6-sulfo N-acetyl glucosamine on both N- and O-linked glycans of CD44 in myeloid cells.
1 Present address: Section of Bone Marrow Transplantation, Rush Presbyterian–St. Luke’s Medical Center, Chicago, IL 60612, USA
2 To whom correspondence should be addressed; E-mail: pauline@interchange.ubc.ca
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