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 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.
Bouma
Gerben
G
Department of Immunology, Erasmus MC, 3015 GE Rotterdam, The Netherlands. g.bouma@erasmsmc.nl
Nikolic
Tatjana
T
Coppens
Jojanneke M C
JM
van Helden-Meeuwsen
Cornelia G
CG
Leenen
Pieter J M
PJ
Drexhage
Hemmo A
HA
Sozzani
Silvano
S
Versnel
Marjan A
MA
D000818:Animals; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D010529:Peritoneal Cavity / Q000473:pathology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016753:Interleukin-10