title: Depletion of macrophages and dendritic cells in ischemic acute kidney injury.
abstract: BACKGROUND
  Inflammation is thought to play a role in ischemic acute kidney injury (AKI). We have demonstrated that macrophage and dendritic cell depletion, using liposome-encapsulated clodronate (LEC), is protective against ischemic AKI.
  
  
  METHODS
  To determine whether macrophages or dendritic cells or both play a role in ischemic AKI, we performed ischemic AKI in CD11b-DTR mice that have a diphtheria toxin (DT)-induced depletion of CD11b cells (macrophages) and CD11c-DTR mice that have a DT-induced depletion of CD11c cells (dendritic cells).
  
  
  RESULTS
  While LEC-treated animals had a significant functional protection from AKI, CD11b-DTR and CD11c-DTR mice were not protected against AKI despite a similar degree of renal macrophage and dendritic cell depletion. Proinflammatory cytokines are known to play a role in ischemic AKI. To determine the possible reasons for the lack of protection in CD11b-DTR and CD11c-DTR mice compared to LEC-treated mice, 32 cytokines/chemokines were measured in these mice. Of the cytokines/chemokines measured, IL-6, MCP-1, GMCSF, IL-1β and CXCL1 (also known as IL-8 in humans or KC in mice) showed significant differences in the LEC-treated, CD11b-DTR and CD11c-DTR mice. MCP-1 and CXCL1 (known mediators of AKI), and also GMCSF and IL-1β were increased in AKI and decreased in LEC-treated AKI but not AKI in CD11b-DTR or CD11c-DTR mice.
  
  
  CONCLUSIONS
  These findings suggest that LEC-mediated protection from AKI is not simply mediated by depletion of renal macrophage or dendritic cell subpopulations. Protection against AKI in LEC-treated compared to CD11b-DTR or CD11c-DTR mice may be partially explained by differences in proinflammatory cytokine profiles.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado at Denver, Aurora, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lu
authors.forename: Sarah
authors.initials: S
authors.lastname: Faubel
authors.forename: Zhibin
authors.initials: Z
authors.lastname: He
authors.forename: Ana
authors.initials: A
authors.lastname: Andres Hernando
authors.forename: Alkesh
authors.initials: A
authors.lastname: Jani
authors.forename: Ross
authors.initials: R
authors.lastname: Kedl
authors.forename: Charles L
authors.initials: CL
authors.lastname: Edelstein
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004167:Diphtheria Toxin / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007511:Ischemia / Q000150:complications; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D016207:Cytokines; D004167:Diphtheria Toxin; D007375:Interleukin-1; D053583:Interleukin-1beta; D004002:Clodronic Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor