1. Inhibition of gelatinase B (matrix metalloprotease-9) activity reduces cellular inflammation and restores function of transplanted pancreatic islets.
- Author
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Lingwal N, Padmasekar M, Samikannu B, Bretzel RG, Preissner KT, Linn T, Lingwal, Neelam, Padmasekar, Manju, Samikannu, Balaji, Bretzel, Reinhard G, Preissner, Klaus T, and Linn, Thomas
- Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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