title: Analysis of TNF-mediated recruitment and activation of glomerular dendritic cells in mouse kidneys by compartment-specific flow cytometry.
abstract: Renal dendritic cells (DCs) form an interstitial network contributing to inflammatory and adaptive immune responses in the kidney. The presence and functional role of DC-like glomerular CD11c(+) mononuclear phagocytes is a matter of debate. Using compartment-specific flow cytometry we found that healthy mouse kidneys contained 1.3 CD11c(+) cells per 100 glomeruli and these increased by 4.6-fold and 13-fold after TNF stimulation and immune complex deposition, respectively. Compartment-specific mRNA expression revealed a predominantly glomerular expression of TNF receptors, chemokines, and adhesion molecules; all upregulated after TNF exposure. Intraperitoneal TNF injection induced influx of neutrophils and mononuclear phagocytes including DC-like CD11c(+) cells into both the glomerular and tubulointerstitial compartments, but reduced in TNF receptor (Tnfr) 1-deficient mice. Additionally, Tnfr2 deficiency impaired glomerular infiltration of CD11c(+) cells, but not neutrophils. Interstitial CD11c(+) cells infiltrated in the presence of Tnfr1 or Tnfr2. TNF exposure also induced similar maturation of glomerular and interstitial CD11c(+) cells as demonstrated by increased surface expression of MHC II, CD54, and costimulatory molecules CD40, CD80, and CD86. Thus, by compartment-specific flow cytometry we could demonstrate the constitutive presence of DC-like CD11c(+) mononuclear phagocytes in normal mouse glomeruli and their TNF-induced accumulation and activation.
authors: Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany.
authors: Martin
authors: M
authors: Schwarz
authors: Anela
authors: A
authors: Taubitz
authors: Nuru
authors: N
authors: Eltrich
authors: Shrikant R
authors: SR
authors: Mulay
authors: Ramanjaneyulu
authors: R
authors: Allam
authors: Volker
authors: V
authors: Vielhauer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002469:Cell Separation / Q000379:methods*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D018836:Inflammation Mediators / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009395:Nephritis, Interstitial / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010586:Phagocytes / Q000276:immunology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: D015415:Biomarkers; D039521:CD11c Antigen; D015815:Cell Adhesion Molecules; D018925:Chemokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha