Role of sulfation in CD44-mediated hyaluronan binding induced by inflammatory mediators in human CD14(+) peripheral blood monocytes.
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 NaClO(3), an inhibitor of sulfation, prevented HA binding in a significant percentage of CD14(+) PBMC induced by TNF-alpha, LPS, IL-1beta, or IFN-gamma. Furthermore, stimulation with TNF-alpha or IFN-gamma in the presence of NaClO(3) 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 NaClO(3), 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.
Brown
K L
KL
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Maiti
A
A
Johnson
P
P
D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D006820:Hyaluronic Acid / Q000378:metabolism*; D018836:Inflammation Mediators / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D009000:Monocytes / Q000378:metabolism*; D010472:Perchlorates / Q000494:pharmacology; D017670:Sodium Compounds / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018960:Hyaluronan Receptors; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D010472:Perchlorates; D017670:Sodium Compounds; D013431:Sulfates; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D006820:Hyaluronic Acid; C031068:sodium perchlorate