title: Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection.
abstract: BACKGROUND
  The association of complement with the progression of acute T cell mediated rejection (ATCMR) is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs) in acute T-cell mediated rejection using rat and human renal allografts.
  
  
  METHODS
  We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR) and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP) by immunohistochemical staining in human renal grafts and their clinical course.
  
  
  RESULTS
  qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry), was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.
  
  
  CONCLUSIONS
  We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yamanaka
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kakuta
authors.affiliation: Division of Organ Transplantation, Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nakazawa
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Taigo
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Imamura
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Okumi
authors.affiliation: Division of Organ Transplantation, Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Division of Organ Transplantation, Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Okuyama
authors.affiliation: Department of Nephrology and Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000378:metabolism*; D018957:CD59 Antigens / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006085:Graft Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D051381:Rats; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018957:CD59 Antigens; C513105:Cr1l protein, rat; D011956:Receptors, Cell Surface; D003165:Complement System Proteins