title: Increased recruitment but impaired function of leukocytes during inflammation in mouse models of type 1 and type 2 diabetes.
abstract: BACKGROUND
  Patients suffering from diabetes show defective bacterial clearance. This study investigates the effects of elevated plasma glucose levels during diabetes on leukocyte recruitment and function in established models of inflammation.
  
  
  RESULTS
  Diabetes was induced in C57Bl/6 mice by intravenous alloxan (causing severe hyperglycemia), or by high fat diet (moderate hyperglycemia). Leukocyte recruitment was studied in anaesthetized mice using intravital microscopy of exposed cremaster muscles, where numbers of rolling, adherent and emigrated leukocytes were quantified before and during exposure to the inflammatory chemokine MIP-2 (0.5 nM). During basal conditions, prior to addition of chemokine, the adherent and emigrated leukocytes were increased in both alloxan- (62±18% and 85±21%, respectively) and high fat diet-induced (77±25% and 86±17%, respectively) diabetes compared to control mice. MIP-2 induced leukocyte emigration in all groups, albeit significantly more cells emigrated in alloxan-treated mice (15.3±1.0) compared to control (8.0±1.1) mice. Bacterial clearance was followed for 10 days after subcutaneous injection of bioluminescent S. aureus using non-invasive IVIS imaging, and the inflammatory response was assessed by Myeloperoxidase-ELISA and confocal imaging. The phagocytic ability of leukocytes was assessed using LPS-coated fluorescent beads and flow cytometry. Despite efficient leukocyte recruitment, alloxan-treated mice demonstrated an impaired ability to clear bacterial infection, which we found correlated to a 50% decreased phagocytic ability of leukocytes in diabetic mice.
  
  
  CONCLUSIONS
  These results indicate that reduced ability to clear bacterial infections observed during experimentally induced diabetes is not due to reduced leukocyte recruitment since sustained hyperglycemia results in increased levels of adherent and emigrated leukocytes in mouse models of type 1 and type 2 diabetes. Instead, decreased phagocytic ability observed for leukocytes isolated from diabetic mice might account for the impaired bacterial clearance.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Ulrika Sofia
authors.initials: US
authors.lastname: Pettersson
authors.forename: Gustaf
authors.initials: G
authors.lastname: Christoffersson
authors.forename: Sara
authors.initials: S
authors.lastname: Massena
authors.forename: David
authors.initials: D
authors.lastname: Ahl
authors.forename: Leif
authors.initials: L
authors.lastname: Jansson
authors.forename: Johanna
authors.initials: J
authors.lastname: Henriksnäs
authors.forename: Mia
authors.initials: M
authors.lastname: Phillipson
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D054426:Chemokine CXCL2 / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000276:immunology / Q000382:microbiology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology
chemical_list: D001786:Blood Glucose; D054426:Chemokine CXCL2