Inhibition of Gelatinase B (Matrix Metalloprotease-9) Activity Reduces Cellular Inflammation and Restores Function of Transplanted Pancreatic Islets

  1. Thomas Linn1
  1. 1Third Medical Department, Faculty of Medicine, Justus-Liebig University, Giessen, Germany
  2. 2Institute for Biochemistry, Faculty of Medicine, Justus-Liebig University, Giessen, Germany
  1. Corresponding author: Thomas Linn, thomas.linn{at}


Islet transplantation provides an approach to compensate for loss of insulin-producing cells in patients with type 1 diabetes. However, the intraportal route of transplantation is associated with instant inflammatory reactions to the graft and subsequent islet destruction as well. Although matrix metalloprotease (MMP)-2 and -9 are involved in both remodeling of extracellular matrix and leukocyte migration, their influence on the outcome of islet transplantation has not been characterized. We observed comparable MMP-2 mRNA expressions in control and transplanted groups of mice, whereas MMP-9 mRNA and protein expression levels increased after islet transplantation. Immunostaining for CD11b (Mac-1)-expressing leukocytes (macrophage, neutrophils) and Ly6G (neutrophils) revealed substantially reduced inflammatory cell migration into islet-transplanted liver in MMP-9 knockout recipients. Moreover, gelatinase inhibition resulted in a significant increase in the insulin content of transplanted pancreatic islets and reduced macrophage and neutrophil influx compared with the control group. These results indicate that the increase of MMP-9 expression and activity after islet transplantation is directly related to enhanced leukocyte migration and that early islet graft survival can be improved by inhibiting MMP-9 (gelatinase B) activity.


  • Received August 17, 2011.
  • Accepted March 9, 2012.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

| Table of Contents

This Article

  1. Diabetes vol. 61 no. 8 2045-2053
  1. Supplementary Data
  2. All Versions of this Article:
    1. db11-1143v1
    2. 61/8/2045 most recent