title: Chemokines and their receptors in human renal allotransplantation.
abstract: BACKGROUND
  Chemokines and their receptors play a critical role in leukocyte trafficking, and inhibition of select chemokines has been shown to attenuate kidney disease and allograft rejection in animal models. Therefore, we evaluated chemokine and chemokine receptor transcripts in human renal allograft biopsies, correlating transcript levels with clinical course and immunohistochemical analysis to relate chemokine expression to relevant clinical human disease phenotypes.
  
  
  METHODS
  Renal biopsies were grouped as postreperfusion (n=10), stable function (n=10), subclinical (n=10) or acute rejection (n=17), or calcineurin inhibitor nephrotoxicity (n=9) based on clinical presentation and histopathologic assessment. Using quantitative real-time polymerase chain reaction analysis, chemokine transcripts were assessed relative to transcript levels in preprocurement biopsies from live donor kidneys (n=15).
  
  
  RESULTS
  Transcripts from several inflammatory chemokines (CCL3, CCL5, CXCL9, CXCL10, and CXCL11) and chemokine receptors (CCR5, CCR7, and CXCR3) were significantly increased in allografts with subclinical and clinical acute rejection, indicating a strong polarization toward a T-helper 1 effector phenotype during rejection. These transcripts also distinguished acutely rejecting allografts from allografts with nonrejection causes of renal dysfunction. Biopsies from patients with stable function without histologic evidence of rejection had increased chemokine transcript levels that were qualitatively similar but quantitatively reduced compared with rejecting allografts.
  
  
  CONCLUSIONS
  This comprehensive evaluation of chemokines and their receptors in human renal transplantation defines associations between chemokine expression and clinical phenotypes, may have diagnostic utility, and highlights relevant pathways for therapeutic intervention.
authors: Emory Transplant Center, Department of Surgery, Emory University, Atlanta, GA, USA.
authors: Denise J
authors: DJ
authors: Lo
authors: Tim A
authors: TA
authors: Weaver
authors: David E
authors: DE
authors: Kleiner
authors: Roslyn B
authors: RB
authors: Mannon
authors: Lynn M
authors: LM
authors: Jacobson
authors: Bryan N
authors: BN
authors: Becker
authors: S John
authors: SJ
authors: Swanson
authors: Douglas A
authors: DA
authors: Hale
authors: Allan D
authors: AD
authors: Kirk
mesh_terms: D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D019743:Chemokines, CXC / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054387:Receptors, CXCR / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D019743:Chemokines, CXC; D054387:Receptors, CXCR