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J. Biol. Chem., Vol. 277, Issue 42, 39343-39349, October 18, 2002

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Immunosuppressive Effects of Glucosamine^*

Linlin Ma, William A. Rudert^§, Jo Harnaha, Marietta Wright^§, Jennifer Machen^§, Robert Lakomy^§, Shiguang Qian, Lina Lu, Paul D. Robbins^¶, Massimo Trucco^§, and Nick Giannoukakis^**

From the  Department of Surgery, T. E. Starzl Transplantation Institute, the Departments of ^¶ Molecular Genetics and Biochemistry and ^** Pathology, and the  Diabetes Institute, University of Pittsburgh School of Medicine, and the ^§ Department of Pediatrics, Division of Immunogenetics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213

Glucosamine is a naturally occurring derivative of glucose and is an essential component of glycoproteins and proteoglycans, important constituents of many eukaryotic proteins. In cells, glucosamine is produced enzymatically by the amidation of glucose 6-phosphate and can then be further modified by acetylation to result in N-acetylglucosamine. Commercially, glucosamine is sold over-the-counter to relieve arthritis. Although there is evidence in favor of the beneficial effects of glucosamine, the mechanism is unknown. Our data demonstrate that glucosamine suppresses the activation of T-lymphoblasts and dendritic cells in vitro as well as allogeneic mixed leukocyte reactivity in a dose-dependent manner. There was no inherent cellular toxicity involved in the inhibition, and the activity was not reproducible with other amine sugars. More importantly, glucosamine administration prolonged allogeneic cardiac allograft survival in vivo. We conclude that, despite its documented effects on insulin sensitivity, glucosamine possesses immunosuppressive activity and could be beneficial as an immunosuppressive agent.

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