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

Diabetes. 2004 Aug;53(8):1979-86. doi: 10.2337/diabetes.53.8.1979.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antigens, CD / blood
  • CD11b Antigen / blood*
  • CD11b Antigen / genetics
  • Calgranulin A / blood*
  • Calgranulin B / blood*
  • Cell Adhesion
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / immunology
  • Female
  • Fibronectins / blood*
  • Flow Cytometry
  • Humans
  • Integrins / blood
  • Male
  • Monocytes / physiology*
  • Rats
  • Reference Values

Substances

  • Antigens, CD
  • CD11b Antigen
  • Calgranulin A
  • Calgranulin B
  • Fibronectins
  • Integrins