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

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...

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Bibliographic Details
Published in:European journal of immunology 2005-01, Vol.35 (1), p.225-235
Main Authors: Bouma, Gerben, Nikolic, Tatjana, Coppens, Jojanneke M C, van Helden-Meeuwsen, Cornelia G, Leenen, Pieter J M, Drexhage, Hemmo A, Sozzani, Silvano, Versnel, Marjan A
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0014-2980