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-gamma mRNA, and the up-regulation of tumor necrosis factor-alpha and interleukin-1beta mRNA in the graft. In vitro studies showed that interleukin-2 and interferon-gamma 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.
CD23 is a surface marker of activated B cells as well as a low-affinity Fc receptor for IgE. In this study, we enumerated CD23-positive peripheral blood lymphocytes and evaluated their clinical significance in patients with IgA nephropathy (IgAN). Twenty-five patients with IgAN and 16 patients with non-IgA proliferative glomerulonephritis (PGN) were studied. Twenty-seven healthy adults served as controls. CD23-bearing cells were enumerated by flow cytometry, and serum IgE levels were measured by latex photometric immunoassay. Significant increases in the number of CD23-positive cells were observed in patients with IgAN (p < 0.01) and PGN (p < 0.05) compared with controls. A significant elevation of serum IgE levels was also observed in the patients with IgAN and PGN (p < 0.05). No positive correlation between the number of CD23-positive cells and serum IgE levels was observed. We also examined the induction of surface CD23 expression on peripheral lymphocytes by interleukin (IL)-2, IL-3, IL-4, IL-5, IL-6, interferon (IFN)-γ IFN-α, phytohemagglutinin, concanavalin A, pokeweed mitogen, lipopolysaccharide and phorbol myristate acetate. IL-4 was revealed to have a significantly potent effect on the induction of cell surface CD23 compared with other stimulants. It was concluded that many patients with IgAN or PGN show high serum IgE levels and/or high CD23-positive cell counts in their peripheral blood, suggesting that hyperactivation of B cells might be involved in the development of IgAN and non-IgA PGN. It appeared that IL-4 may play a significant role in the etiology of these types of glomerulonephritis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.