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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
Ist Teil von
Diabetes (New York, N.Y.), 2004-08, Vol.53 (8), p.1979-1986
Ort / Verlag
Alexandria, VA: American Diabetes Association
Erscheinungsjahr
2004
Quelle
MEDLINE
Beschreibungen/Notizen
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
Gerben Bouma ,
Wai Kwan Lam-Tse ,
Annet F. Wierenga-Wolf ,
Hemmo A. Drexhage and
Marjan A. Versnel
From the Department of Immunology, Erasmus MC, Rotterdam, the Netherlands
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
Accepted April 29, 2004.
Received November 12, 2003.
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