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(American Journal of Pathology. 2000;157:825-831.)
© 2000 American Society for Investigative Pathology

Regular Articles

In Situ Localization of C3 Synthesis in Experimental Acute Renal Allograft Rejection

Julian R. Pratt^*, Katsushige Abe, Masanabu Miyazaki, Wuding Zhou^* and Steven H. Sacks^*

From the Department of Nephrology and Transplantation,^*
King’s College, University of London, Guy’s Hospital, London, United Kingdom; and the Second Department of Internal Medicine,
Nagasaki University School of Medicine, Nagasaki, Japan

Recent evidence has implicated complement in renal transplant injury and identified the kidney as a source of complement components. We therefore investigated the local gene expression of complement component C3, pivotal to complement activation pathways and a mediator of inflammatory injury, in a rat renal transplant model. By reverse transcriptase-polymerase chain reaction, the expression of C3 mRNA increased in two phases. The first phase coincided with post-ischemic injury over 2 days post-transplantation and was localized by in situ hybridization to vessels and glomerular mesangial cells in allogeneic and syngeneic (control) kidney transplants. In allografts only, a second phase was found in tubular epithelial cells, glomerular parietal cells, vessel walls and some infiltrating cells, which peaked on day 4 together with rapid influx of leukocytes, tubule cell damage, the induction of interleukin-2 and interferon- mRNA, and the up-regulation of tumor necrosis factor- and interleukin-1ß mRNA in the graft. In vitro studies showed that interleukin-2 and interferon- up-regulate C3 production in renal tubule cells. We conclude that post-ischemic injury led to transient up-regulation of glomerular expression of C3 mRNA. Subsequent cellular rejection was associated with tubulointerstitial/glomerular parietal cell expression of C3 mRNA. This differential expression of local C3, immediately post-transplant or associated with acute rejection, may have implications for putative therapeutic complement inhibition in clinical transplantation.

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