The role of cytotoxic macrophages in non-obese diabetic mice: cytotoxicity against murine mastocytoma and beta-cell lines

A. Kasuga, T. Maruyama, I. Takei, A. Shimada, T. Kasatani, K. Watanabe, T. Saruta, T. Nakaki, S. Habu, J. Miyazaki

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19 Citations (Scopus)

Abstract

The cytotoxicity of macrophages from non-obese diabetic (NOD) mice against murine mastocytoma (P-815), and murine beta-cell lines having the NOD gene background (MIN6N-9a), were examined. Peritoneal exudate cells from 20-week-old mice showed higher cytotoxicity, measured as inhibition of thymidine uptake into P-815, than those from 12-week-old mice (p <0.01). In cyclophosphamide-injected mice, cytotoxicity of peritoneal exudate cells had increased at 8 days post-injection, at which time the mice were not diabetic. To confirm macrophage cytotoxicity against pancreatic cells and examine its cytolytic mechanism, the cytotoxicity of peritoneal exudate cells from cyclophosphamide-injected NOD mice against MIN6N-9a cells was measured by the chromium release assay. These peritoneal exudate cells showed higher cytotoxicity as compared to those of saline-injected mice (p <0.001). Macrophages were demonstrated to be the major component of peritoneal exudate cells (50%) by flowcytometric analyses. Cytotoxicity increased with macrophage enrichment by adhesion (p <0.01). Furthermore, a macrophage toxin, silica, completely blocked the cytotoxicity (p <0.001). Cytokines (interleukin 1 and tumour necrosis factor) and a nitric-oxide-producing vasodilator, sodium nitroprusside, were cytotoxic to MIN6N-9a cells but only sodium nitroprusside showed cytotoxicity when incubated for the same period as peritoneal exudate cells. Thus, macrophages play an important role in beta-cell destruction and soluble factors other than cytokines (e.g. nitric oxide) may be mediators of this early cytolytic process.

Original languageEnglish
Pages (from-to)1252-1257
Number of pages6
JournalDiabetologia
Volume36
Issue number12
DOIs
Publication statusPublished - 1993 Dec 1

Keywords

  • Non-obese diabetic mice
  • Type 1 (insulin-dependent) diabetes mellitus
  • cytokine
  • macrophage
  • nitric oxide

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Kasuga, A., Maruyama, T., Takei, I., Shimada, A., Kasatani, T., Watanabe, K., Saruta, T., Nakaki, T., Habu, S., & Miyazaki, J. (1993). The role of cytotoxic macrophages in non-obese diabetic mice: cytotoxicity against murine mastocytoma and beta-cell lines. Diabetologia, 36(12), 1252-1257. https://doi.org/10.1007/BF00400802