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The Journal of Immunology, 2001, 167: 5367-5374.
Copyright © 2001 by The American Association of Immunologists

Role of Sulfation in CD44-Mediated Hyaluronan Binding Induced by Inflammatory Mediators in Human CD14+ Peripheral Blood Monocytes1

Kelly L. Brown, Arpita Maiti2 and Pauline Johnson3

Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada

Activation of T cells by Ag or stimulation of monocytes with inflammatory cytokines induces CD44 to bind to hyaluronan (HA), an adhesion event implicated in leukocyte-leukocyte, leukocyte-endothelial cell, and leukocyte-stromal cell interactions. We have previously shown that TNF-{alpha} induces CD44 sulfation in a leukemic cell line, which correlated with the induction of HA binding and CD44-mediated adhesion. In this study, we establish that TNF-{alpha} and IFN-{gamma} induce HA binding and the sulfation of CD44 in CD14+ PBMC, whereas no induced HA binding or CD44 sulfation was observed in CD14- PBMC stimulated with TNF-{alpha}. Treatment of cells with NaClO3, an inhibitor of sulfation, prevented HA binding in a significant percentage of CD14+ PBMC induced by TNF-{alpha}, LPS, IL-1{beta}, or IFN-{gamma}. Furthermore, stimulation with TNF-{alpha} or IFN-{gamma} in the presence of NaClO3 reduced the ability of isolated CD44H to bind HA, demonstrating a direct effect of CD44H sulfation on HA binding. In contrast, the transient induction of HA binding in T cells by PHA was not affected by NaClO3, suggesting that activated T cells do not use sulfation as a mechanism to regulate HA binding. Overall, these results demonstrate that inducible sulfation of CD44H is one mechanism used by CD14+ peripheral blood monocytes to induce HA binding in response to inflammatory agents such as TNF-{alpha} and IFN-{gamma}.




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