title: Local complement C3 expression is upregulated in humoral and cellular rejection of renal allografts.
abstract: Evidence on the role of the complement system in transplantation pathology has been accelerated by the discovery of C4d as an in situ marker of antibody-mediated rejection. However, a local or systemic source of complement expression during acute rejection is under discussion. Thus, we quantitatively analyzed local RNA expression of complement component C3 as a pivotal molecule in active humoral and cellular rejection of renal allografts. After laser microdissection, real-time RT-PCR was performed for C3 using RNA extracted from tubuli and glomeruli of 68 paraffin-embedded renal allograft biopsies. Protocol and indication biopsies with signs of humoral and/or cellular rejection were investigated. Quantitative expression analysis of cytokines (IFN gamma, MCP-1, IL2, IL8) potentially influencing local C3 expression was performed. We observed a significant increase in median expression level of C3 mRNA in tubuli of C4d-positive indication biopsies, and in tubuli from indication biopsies with signs of T-cell-mediated cellular rejection. Highest expression levels were found in C4d-positive indication biopsies with signs of cellular rejection. Biopsies with upregulated C3 showed increased IFN gamma expression, suggesting allograft-infiltrating T-cells as potential stimulus for local C3 expression. Therefore, locally synthesized complement component C3 contributes to both humoral and cellular rejection, with tubular epithelial cells being a major source.
authors.affiliation: Department of Pathology, Medizinische Hochschule Hannover, Germany.
authors.forename: Ebru
authors.initials: E
authors.lastname: Serinsöz
authors.forename: Oliver
authors.initials: O
authors.lastname: Bock
authors.forename: Wilfried
authors.initials: W
authors.lastname: Gwinner
authors.forename: Anke
authors.initials: A
authors.lastname: Schwarz
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
mesh_terms: D001706:Biopsy; D003176:Complement C3 / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006084:Graft Rejection / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous; D015854:Up-Regulation
chemical_list: D003176:Complement C3; D016207:Cytokines; D012333:RNA, Messenger