Tumor necrosis factor-alpha modifies adhesion properties of rat islet B cells

J Clin Invest. 1993 May;91(5):1868-76. doi: 10.1172/JCI116403.

Abstract

The characteristic three-dimensional cell type organization of islets of Langerhans is perturbed in animal models of diabetes, suggesting that it may be important for islet function. Rat islet cells in culture are able to form aggregates with an architecture similar to native islets (pseudoislets), thus providing a good model to study the molecular basis of islet architecture and its role in islet function. Sorted islet B cells and non-B cells were permanently labeled with two different fluorescent dyes (DiO and DiI), mixed, and allowed to form aggregates during a 5-d culture in the presence or absence of TNF-alpha (100 U/ml), a cytokine suggested to be implicated in the early physiological events leading to insulin-dependent diabetes mellitus. Confocal microscopy of aggregates revealed that TNF-alpha reversibly perturbs the typical segregation between B and non-B cells. Insulin secretion, was altered in the disorganized aggregates, and returned towards normal when pseudoislets had regained their typical architecture. The homotypic adhesion properties of sorted B and non-B cells cultured for 20 h in the presence or absence of TNF-alpha were studied in a short term aggregation assay. TNF-alpha induced a significant rise in Ca(2+)-independent adhesion of B cells (from 24 +/- 1.1% to 44.3 +/- 1.2%; n = 4, P < 0.001). These findings raise the possibility that the increased expression of Ca(2+)-independent adhesion molecules on B cells leads to altered islet architecture, which might be a factor in the perturbation of islet function induced by TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / pharmacology
  • Cell Adhesion / drug effects*
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Aggregation / drug effects
  • Cells, Cultured
  • Egtazic Acid / pharmacology
  • Flow Cytometry / methods
  • Glucose / pharmacology
  • Insulin / metabolism
  • Insulin Secretion
  • Intercellular Adhesion Molecule-1
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiology*
  • Kinetics
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Pancreas / cytology
  • Pancreas / drug effects
  • Pancreas / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Insulin
  • Lymphocyte Function-Associated Antigen-1
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Egtazic Acid
  • Glucose
  • Calcium