title: Monocyte- and endothelial-derived microparticles induce an inflammatory phenotype in human podocytes.
abstract: OBJECTIVE
  Proteinuria is associated with cardiovascular and chronic kidney disease. Microparticles (MPs) are bioactive vesicles shed from activated cells and also linked to cardiovascular disease. MP-like structures have been identified in the glomerular basement membrane, urinary space and between the glomerular basement membrane and the podocyte. We hypothesised that circulating MPs may provide a link between vascular injury and kidney diseases by inducing podocyte phenotypic alterations, thus propagating glomerular dysfunction and proteinuria.
  
  
  METHODS
  Human umbilical vein endothelial cells and U937 monocytes were stimulated with TNF-α to produce MPs. These MPs were confirmed by electron microscopy, and added to differentiated podocyte monolayers to determine effects on podocyte albumin endocytosis and the production of soluble mediators.
  
  
  RESULTS
  Monocyte and endothelial MPs upregulated podocyte production of pro-inflammatory mediators monocyte chemoattractant protein-1 (p < 0.001) and interleukin-6 (p < 0.001). Only monocyte MPs upregulated podocyte secretion of VEGF (p < 0.001), known to regulate glomerular permeability. Endothelial MPs decreased podocyte albumin endocytosis by 13% compared to control cells (p < 0.01).
  
  
  CONCLUSIONS
  MPs alter endocytic functions of podocytes and induce secretion of pro-inflammatory cytokines, potentially leading to glomerular inflammation in vivo and the development of proteinuria. This study identifies a potential pathophysiological role for circulating MPs in the kidney through effects on the podocyte.
authors.affiliation: Department of Infection, Immunity and Inflammation, Faculty of Medicine and Biological Sciences, University of Leicester, UK.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Eyre
authors.forename: James O
authors.initials: JO
authors.lastname: Burton
authors.forename: Moin A
authors.initials: MA
authors.lastname: Saleem
authors.forename: Peter W
authors.initials: PW
authors.lastname: Mathieson
authors.forename: Peter S
authors.initials: PS
authors.lastname: Topham
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Brunskill
mesh_terms: D000418:Albumins / Q000378:metabolism; D042702:Angiopoietin-2 / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000473:pathology* / Q000502:physiology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D005921:Glomerulonephritis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009000:Monocytes / Q000473:pathology / Q000502:physiology; D010641:Phenotype; D050199:Podocytes / Q000473:pathology* / Q000502:physiology*; D011507:Proteinuria / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D020298:U937 Cells; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000418:Albumins; D042702:Angiopoietin-2; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat