Bovine Islets Are Less Susceptible Than Human Islets to Damage by Human Cytokines

Transplantation. 2001 Jan 15;71(1):21-6. doi: 10.1097/00007890-200101150-00004.

Abstract

Background: The potential benefits of islet xenografting in type 1 diabetes include the intriguing, but still unanswered, possibility that the grafted xenoislets may be less subjected to human autoimmune attack. Cytokines may play a major role in the pathogenesis of autoimmune diabetes by causing impairment of insulin release and pancreatic islet cell toxicity.

Methods: We compared insulin secretion, islet cell death and survival, inducible nitric oxide synthase (iNOS) mRNA expression, nitrite production, and Bcl-2 and Bax mRNA expression in isolated human and large mammal (bovine) islets exposed to 50 U/ml recombinant human interleukin-1, 1,000 U/ml recombinant human tumor necrosis factor-alpha and 1,000 U/ml recombinant human interferon-gamma.

Results: After 24-hr exposure, a marked decrease of glucose-stimulated insulin secretion was observed with human, but not with bovine islets. After 48-hr exposure, human, but not bovine, pancreatic islets showed a significantly higher percentage of apoptotic cells compared to controls. Treatment of human islets with human cytokines induced up-regulation of iNOS mRNA, increased levels of nitrites, and down-regulation of Bcl-2 mRNA, with unchanged levels of Bax mRNA. These parameters were not affected by cytokines in bovine islets.

Conclusions: Bovine islets are less susceptible than human islets to the effects of human cytokines, which may be a potential advantage of xenotransplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cattle
  • Cell Survival / drug effects
  • Cytokines / pharmacology*
  • Gene Expression
  • Genes, bcl-2 / genetics
  • Humans
  • In Situ Nick-End Labeling
  • Insulin / metabolism
  • Insulin Secretion
  • Interleukin-1 / pharmacology
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects*
  • Necrosis
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type II
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / pharmacology
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Cytokines
  • Insulin
  • Interleukin-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II