NOD mice have a severely impaired ability to recruit leukocytes into sites of inflammation

Eur J Immunol. 2005 Jan;35(1):225-35. doi: 10.1002/eji.200425513.

Abstract

The accumulation of macrophages (M Phi) and dendritic cells (DC) in the pancreas plays a crucial role in the pathogenesis of autoimmune diabetes. We studied the recruitment of monocytes, M Phi and DC to sites of inflammation, i.e. the peritoneal cavity and a subcutaneously elicited air pouch in the NOD mouse model of autoimmune diabetes. The leukocyte recruitment was studied from 1 to 7 days after injection of thioglycollate (peritoneum), C5a (peritoneum, air pouch), CCL2 and CCL3 (air pouch). C57BL/6 and BALB/c mice served as controls. Morphological and flow cytometric analysis of the recruited cells was performed, IL-1 beta, TNF-alpha, IL-6, IL-12 and IL-10 in exudates measured, and in vitro CCL2-chemotaxis of exudate M Phi (Boyden chamber) determined. NOD mice were strongly impaired in the recruitment of M Phi, DC, monocytes, and granulocytes. Chemokine-injected air pouches of NOD mice showed an increased IL-10 and a decreased IL-1 beta level, while the other cytokines were normally or very lowly expressed. In addition, NOD exudate M Phi displayed an impaired in vitro CCL2-induced migration. Our data show that NOD mice have an impaired ability to recruit leukocytes into sites of inflammation elicited in the peritoneum and the air pouch. A raised IL-10/IL-1 beta ratio at these sites and a deficient migratory capacity of NOD monocytes are important determinants in this impairment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Chemokine CCL2 / pharmacology
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology
  • Female
  • Immunity, Innate
  • In Vitro Techniques
  • Inflammation / immunology*
  • Inflammation / pathology
  • Interleukin-10 / metabolism
  • Leukocytes / drug effects
  • Leukocytes / immunology*
  • Leukocytes / pathology
  • Macrophages / immunology
  • Macrophages / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Monocytes / immunology
  • Monocytes / pathology
  • Peritoneal Cavity / pathology

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Interleukin-10