Increased Serum Levels of MRP-8/14 in Type 1 Diabetes Induce an Increased Expression of CD11b and an Enhanced Adhesion of Circulating Monocytes to Fibronectin
- Address correspondence and reprint requests to Dr. Gerben Bouma, Dept. of Immunology, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, Netherlands. E-mail: g.bouma{at}erasmusmc.nl
Abstract
The recruitment of monocytes from the bloodstream is crucial in the accumulation of macrophages and dendritic cells in type 1 diabetic pancreases. Adhesion via integrins to endothelium and extracellular matrix proteins, such as fibronectin (FN), and the production of myeloid-related protein (MRP)-8, -14, and -8/14 by recently transmigrated monocytes are thought to be instrumental in such recruitment. We determined the FN-adhesive capacity and integrin expression of monocytes of type 1 and type 2 diabetic patients and related them to the subjects’ serum levels of MRP-8, -14 and -8/14. Monocytes of type 1 diabetic patients displayed an increased adhesion to fibronectin in comparison with type 2 patients and healthy control subjects but had a normal expression of the FN binding integrins CD29, CD49a, CD49d, and CD49e (although CD11b and CD18 expression was increased). MRP-8/14, which was increased in the sera of type 1 diabetic patients, induced healthy donor monocytes to adhere to FN and upregulate CD11b expression in a dosage-dependent manner. The observed MRP-induced increased adhesion of monocytes to FN and upregulation of CD11b most likely contributed to a facilitated accumulation of monocytes and monocyte-derived cells at the site of inflammation, in this case the pancreatic islets.
- APC, antigen-presenting cell
- DC, dendritic cell
- ECM, extracellular matrix
- ELISA, enzyme-linked immunosorbent assay
- fMLP, N-formyl-methionyl-leucyl-phenylalanine
- FN, fibronectin
- IL, interleukin
- LFA-1, leukocyte function antigen-1
- MRP, myeloid-related protein
- NF-κB, nuclear factor-κB
- VLA, very late antigen
Footnotes
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- Accepted April 29, 2004.
- Received November 12, 2003.
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