Inhibition of gelatinase B (matrix metalloprotease-9) activity reduces cellular inflammation and restores function of transplanted pancreatic islets

Neelam Lingwal, Manju Padmasekar, Balaji Samikannu, Reinhard G. Bretzel, Klaus T. Preissner, Thomas Linn

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2045-2053
Number of pages9
JournalDiabetes
Volume61
Issue number8
DOIs
Publication statusPublished - 1 Aug 2012
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 9
Metalloproteases
Islets of Langerhans
Islets of Langerhans Transplantation
Inflammation
Neutrophils
Leukocytes
Macrophages
Insulin
Gelatinases
Control Groups
Messenger RNA
Graft Survival
Type 1 Diabetes Mellitus
Cell Movement
Extracellular Matrix
Transplantation
Transplants
Liver
Proteins

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Inhibition of gelatinase B (matrix metalloprotease-9) activity reduces cellular inflammation and restores function of transplanted pancreatic islets. / Lingwal, Neelam; Padmasekar, Manju; Samikannu, Balaji; Bretzel, Reinhard G.; Preissner, Klaus T.; Linn, Thomas.

In: Diabetes, Vol. 61, No. 8, 01.08.2012, p. 2045-2053.

Research output: Contribution to journalArticle

Lingwal, Neelam ; Padmasekar, Manju ; Samikannu, Balaji ; Bretzel, Reinhard G. ; Preissner, Klaus T. ; Linn, Thomas. / Inhibition of gelatinase B (matrix metalloprotease-9) activity reduces cellular inflammation and restores function of transplanted pancreatic islets. In: Diabetes. 2012 ; Vol. 61, No. 8. pp. 2045-2053.
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