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Diabetes 53:1452-1458, 2004
© 2004 by the American Diabetes Association, Inc.

Advanced Glycation End Products Modulate the Maturation and Function of Peripheral Blood Dendritic Cells

Claire L. Price1, Patrick S. Sharp2, Margaret E. North1, Sandra J. Rainbow3, and Stella C. Knight1

1 Antigen Presentation Research Group, Faculty of Medicine, Imperial College London, Middlesex, U.K
2 Department of Endocrinology and Diabetes, Northwick Park Hospital, Middlesex, U.K
3 Department of Clinical Biochemistry, Northwick Park Hospital, Middlesex, U.K

Advanced glycation end products (AGEs), a complex and heterogeneous group of posttranslational modifications of proteins in vivo, have been widely studied for their involvement in diabetic complications; these complications are largely vascular and accompanied by inflammation. Because dendritic cells (DCs) initiate and modulate inflammatory responses, we hypothesized that AGEs might exert immunomodulatory effects via antigen-presenting DCs. To test this hypothesis, we investigated effects of the AGE peptide, compared with the naked peptide, on maturation, costimulatory molecule expression, and function of DCs in peripheral blood. From flow cytometry, we found a dose-dependent inhibition in CD83 expression on DCs exposed for 2.5 h to each of two synthetic AGE peptides. A similar culture for 24 h additionally produced an inhibition of CD80 expression, whereas exposure to AGEs for 3 days induced a large increase in DC numbers and a concomitant loss of monocyte/macrophages. Exposure of DCs to AGEs resulted in a dose-dependent loss in their capacity to stimulate primary proliferation of allogeneic T-cells. We conclude that AGEs promote development of DCs but that these DCs fail to express maturation markers and lose the capacity to stimulate primary T-cell responses. Effects of AGEs on DCs could be instrumental in the immunological changes associated with diabetes.

Address correspondence and reprint requests to Prof. S.C. Knight, Antigen Presentation Research Group, Faculty of Medicine Imperial College London, Northwick ParkSt Marks Campus, Level 7W, St. Marks Hospital, Watford Road, Harrow, Middlesex, HA1 3UJ, U.K. E-mail: s.knight{at}imperial.ac.uk


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.