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

Abstract

The accumulation of macrophages (Mφ) and dendritic cells (DC) in the pancreas plays a crucial role in the pathogenesis of autoimmune diabetes. We studied the recruitment of monocytes, Mφ 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-1β, TNF-α, IL-6, IL-12 and IL-10 in exudates measured, and in vitro CCL2-chemotaxis of exudate Mφ (Boyden chamber) determined. NOD mice were strongly impaired in the recruitment of Mφ, DC, monocytes, and granulocytes. Chemokine-injected air pouches of NOD mice showed an increased IL-10 and a decreased IL-1β level, while the other cytokines were normally or very lowly expressed. In addition, NOD exudate Mφ 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-1β ratio at these sites and a deficient migratory capacity of NOD monocytes are important determinants in this impairment. © 2005 Wiley-VCH GmbH & Co. KGaA, Weinheim.