title: Novel insights in localization and expression levels of C5aR and C5L2 under native and post-transplant conditions in the kidney.
abstract: OBJECTIVE
  The complement system, and especially C5a, plays an important role in the pathophysiology of renal diseases and post-transplant renal injury. The two receptors for C5a are C5a receptor (C5aR) and C5a-like-receptor-2 (C5L2). Only renal C5aR expression has been reported, although exact localization and alterations in expression after transplantation are unknown.
  
  
  RESULTS
  Renal C5aR and C5L2 expression and localization were analyzed immunohistochemically. C5aR and C5L2 expression was analyzed in human kidney biopsies obtained from living donors and patients suffering from acute tubular necrosis, acute cellular and vascular rejection or IF/TA. C5aR was expressed in the thick ascending limb of Henle's loop and first part of the distal convoluted tubule (DCT). Under inflammatory conditions, C5aR was de novo expressed in proximal tubuli. C5L2 was expressed in the kidney and localized to DCT1, DCT2 and connecting tubule. Persistent distal tubular expression of both receptors was demonstrated after renal transplantation.
  
  
  CONCLUSIONS
  This study shows distinct renal expression patterns for C5aR and C5L2. Our findings suggest a functional role for renal C5L2 rather than being a C5a decoy receptor. Future studies focusing on renal C5a-C5aR interaction should take differential C5aR and C5L2 expression into account, alongside abundant C5aR expression on infiltrating cells.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Postbus 30001, 9700 RB Groningen, The Netherlands. m.b.van.werkhoven@umcg.nl
authors.forename: Maaike B
authors.initials: MB
authors.lastname: van Werkhoven
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Damman
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: Christina
authors.initials: C
authors.lastname: Krikke
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van Son
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
authors.forename: Marcory C R F
authors.initials: MC
authors.lastname: van Dijk
authors.forename: Marc A J
authors.initials: MA
authors.lastname: Seelen
mesh_terms: D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007674:Kidney Diseases / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000276:immunology / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine / Q000378:metabolism*; D011951:Receptors, Complement / Q000378:metabolism*
chemical_list: C488033:C5AR1 protein, human; C417003:C5aR2 protein, human; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; D011951:Receptors, Complement