title: NOD mice have a severely impaired ability to recruit leukocytes into sites of inflammation.
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.
authors.affiliation: Department of Immunology, Erasmus MC, 3015 GE Rotterdam, The Netherlands. g.bouma@erasmsmc.nl
authors.forename: Gerben
authors.initials: G
authors.lastname: Bouma
authors.forename: Tatjana
authors.initials: T
authors.lastname: Nikolic
authors.forename: Jojanneke M C
authors.initials: JM
authors.lastname: Coppens
authors.forename: Cornelia G
authors.initials: CG
authors.lastname: van Helden-Meeuwsen
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.forename: Marjan A
authors.initials: MA
authors.lastname: Versnel
mesh_terms: 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
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016753:Interleukin-10