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

Abstract

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-α 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-α and IFN-γ 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-α. Treatment of cells with NaClO3, an inhibitor of sulfation, prevented HA binding in a significant percentage of CD14+ PBMC induced by TNF-α, LPS, IL-1β, or IFN-γ. Furthermore, stimulation with TNF-α or IFN-γ 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-α and IFN-γ.