Local complement C3 expression is upregulated in humoral and cellular rejection of renal allografts.
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.
Serinsöz
Ebru
E
Department of Pathology, Medizinische Hochschule Hannover, Germany.
Bock
Oliver
O
Gwinner
Wilfried
W
Schwarz
Anke
A
Haller
Hermann
H
Kreipe
Hans
H
Mengel
Michael
M
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
D003176:Complement C3; D016207:Cytokines; D012333:RNA, Messenger