Leukocyte extravasation into the pancreatic tissue in transgenic mice expressing interleukln 10 in the islets of langerhans

Lise Wogensen, Xiaojian Huang, Nora Sarvetnick

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

Transgenic expression of interleukin 10 (IL-10) in the islets of Langerhans leads to a pronounced pancreatic inflammation, without inflammation of the islets of Langerhans and without diabetes. A scattered infiltration of macrophages (Mϕ) precedes localized accumulations of CD4+ and CD8+ T lymphocytes, B lymphocytes, and Mϕ. This recruitment of inflammatory cells to the pancreas is somewhat surprising, since the biological activities of IL-10 in vitro indicate that IL-10 is a powerful immunosuppressive cytokine. Since endothelial cells play a major role in leukocyte extravasation, we examined if vascular changes and extralymphoid induction of peripheral and mucosal type vascular addressins contributed to IL-10-induced homing of mononudear cells to the pancreas. The endothelium lining small vessds was highly activated in areas of inflammation, as the endothelial cells became cuboidal, and exhibited increased expression of major histocompatibility complex dass II (Ia), intercellular adhesion molecule 1, and von Willebrand Factor. Furthermore, induction of vascular addressins simultaneously with accumulation of mononuclear cells around islets and vessels indicated that the endothelial cells take on the phenotype of differentiated endothelium specialized for leukocyte extravasation. In conclusion, pancreatic inflammation and vascular changes are prominent in IL-10 transgenic mice. We hypothesize that IL-10, in addition to its immuno-inhibitory properties, is a potent recruitment signal for leukocyte migration in vivo. These effects are relevant for in vivo therapeutic applications of IL-10.

Original languageEnglish (US)
Pages (from-to)175-185
Number of pages11
JournalJournal of Experimental Medicine
Volume178
Issue number1
DOIs
StatePublished - Jul 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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