Intercellular adhesion molecule 1 is induced on isolated endocrine islet cells by cytokines but not by reovirus infection

Iain L. Campbell, Angelina Cutri, David Wilkinson, Andrew W. Boyd, Leonard C. Harrison

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80 Citations (Scopus)

Abstract

The selective destruction of the pancreatic islet beta cells in type 1 diabetes mellitus is thought to be mediated by a cellular autoimmune process, possibly triggered by virus infection in genetically susceptible individuals. Because of the potentially important role of cell-cell adhesion in the immune response, we investigated whether cytokine products of mononuclear cells, or virus infection, induced the expression of intercellular adhesion molecule 1 (ICAM-1) on human endocrine islet cells. By flow cytofluorimetry, control islet cells did not express detectable ICAM-1. However, after a 72-hr exposure of islets to interferon γ (IFN-γ) and/or tumor necrosis factor α (TNF-α) (each at 250 units/ml), ICAM-1 was induced on > 85% of islet cells. IFN-γ was 50% more potent than TNF-α; together, their effects were additive. Class I major histocompatibility complex (MHC) protein expression, detected on control islet cells, was also stimulated by IFN-γ and/or TNF-α. In contrast, infection with reovirus type 3 did not induce ICAM-1 on islet cells, although it stimulated the expression of class I MHC proteins. By double-label indirect immunofluorescence microscopy, ICAM-1 expression was identified on both beta (insulin-secreting) and delta (somatostatin-secreting) islet cells. Monoclonal antibody to ICAM-1 precipitated protein of M(r) 97,000 from [³⁵S]methionine-labeled islets exposed to IFN-γ and TNF-α, but not from control islets. RNA blot analysis revealed a major species of 3.3 kilobases and a minor species of 2.2 kilobases induced in islets exposed to the cytokines. These findings have implications for the molecular mechanisms of beta-cell destruction in type 1 diabetes, in that expression of ICAM-1 by beta cells may facilitate adhesion of antigen-targeted immune cells.
Original languageEnglish
Pages (from-to)4282-4286
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number11
DOIs
Publication statusPublished - 1989
Externally publishedYes

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