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Published online before print November 21, 2003

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(Journal of Leukocyte Biology. 2004;75:307-313.)
© 2004 by Society for Leukocyte Biology

Desialylation of glycoconjugates on the surface of monocytes activates the extracellular signal-related kinases ERK 1/2 and results in enhanced production of specific cytokines

Nicholas M. Stamatos^*,,1, Sabrina Curreli^*, Davide Zella^* and Alan S. Cross

^* Institute of Human Virology and
Division of Infectious Diseases, Department of Medicine, University of Maryland Medical Center, University of Maryland, Baltimore

¹ Correspondence: Institute of Human Virology, University of Maryland Medical System, 725 West Lombard St., Baltimore, MD 21201. E-mail: stamatos{at}umbi.umd.edu

Modulation of the sialic acid content of cell-surface glycoproteins and glycolipids influences the functional capacity of cells of the immune system. The role of sialidase(s) and the consequent desialylation of cell surface glycoconjugates in the activation of monocytes have not been established. In this study, we show that desialylation of glycoconjugates on the surface of purified monocytes using exogenous neuraminidase (NANase) activated extracellular signal-regulated kinase 1/2 (ERK 1/2), an intermediate in intracellular signaling pathways. Elevated levels of phosphorylated ERK 1/2 were detected in desialylated monocytes after 2 h of NANase treatment, and increased amounts persisted for at least 2 additional hours. Desialylation of cell surface glycoconjugates also led to increased production of interleukin (IL)-6, macrophage inflammatory protein (MIP)-1, and MIP-1ß by NANase-treated monocytes that were maintained in culture. Neither increased levels of phosphorylated ERK 1/2 nor enhanced production of cytokines were detected when NANase was heat-inactivated before use, demonstrating the specificity of NANase action. Treatment of monocytes with gram-negative bacterial lipopolysaccharide (LPS) also led to enhanced production of IL-6, MIP-1, and MIP-1ß. The amount of each of these cytokines that was produced was markedly increased when monocytes were desialylated with NANase before exposure to LPS. These results suggest that changes in the sialic acid content of surface glycoconjugates influence the activation of monocytes.

Key Words: sialidase • cellular activation • IL-6 • LPS

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