Advanced glycation end products modulate the maturation and function of peripheral blood dendritic cells.
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.
Price
Claire L
CL
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, UK.
Sharp
Patrick S
PS
North
Margaret E
ME
Rainbow
Sandra J
SJ
Knight
Stella C
SC
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D015703:Antigens, CD; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002452:Cell Count; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D010446:Peptide Fragments / Q000494:pharmacology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000097802:CD83 Antigen
D000324:Adrenocorticotropic Hormone; D015703:Antigens, CD; D004338:Drug Combinations; D017127:Glycation End Products, Advanced; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000097802:CD83 Antigen; C011394:ACTH (4-10)