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

Autor: Pieter J. M. Leenen, Cornelia G van Helden-Meeuwsen, Tatjana Nikolic, Gerben Bouma, Jojanneke M. C. Coppens, Silvano Sozzani, Hemmo A. Drexhage, Marjan A. Versnel
Přispěvatelé: Immunology
Rok vydání: 2005
Předmět:
Zdroj: European Journal of Immunology, 35(1), 225-235. Wiley-VCH
ISSN: 1521-4141
0014-2980
DOI: 10.1002/eji.200425513
Popis: 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.
Databáze: OpenAIRE