Abstract
BackgroundThe role of circulating complement in host defense and immune disease is well established. Although a number of cells and tissues are capable of synthesizing complement components locally, the importance of such local synthesis in immune disease has been difficult to establish.Methodology/Principal FindingsWe used bone marrow transplantation (BMT) between C3 knockout (C3KO) and wild type (WT) mice to construct animals that were discordant for systemic (hepatic) and local (monocytic) C3 synthetic capacity. An immune complex glomerulonephritis (GN) was then induced using intraperitoneal injections of horse spleen apoferritin (HSA) with a lipopolysaccharide (LPS) adjuvant. All HSA/LPS animals developed a proliferative GN with glomerular infiltration by monocytes. By sensitive ELISA, monocyte C3 synthesis could be detected in C3KO animals transplanted with WT bone marrow cells. Despite this, there were no significant differences among groups of mice in measures of clinical (proteinuria, renal function) or histologic (glomerular cellularity, crescents) disease severity.Conclusions/SignificanceIn this model of GN, local synthesis of C3 by infiltrating cells does not appear to be of pathologic importance.
Highlights
The complement proteins are major effectors of inflammation in glomerulonephritis, both in humans and in animal models
Background staining of CD14 in either a wild type (WT) or a C3 knockout (C3KO) mouse treated with saline is shown is Figure 3a–b
As we have shown previously in intact animals [3], there was evidence of C3 glomerular deposition in each chimera with a wild type background (WTIR/WT and WTIR/C3KO; Figure 4)
Summary
The complement proteins are major effectors of inflammation in glomerulonephritis, both in humans and in animal models. The bulk of complement deposited in the glomerulus in acute glomerulonephritis is presumed to come from the circulation, and is synthesized in the liver. A variety of other cells, are capable of synthesizing complement components. There is good evidence that hematopoietic cells of the monocyte/macrophage lineage synthesize a variety of complement components, both in vivo and in vitro [4]. The role of circulating complement in host defense and immune disease is well established. A number of cells and tissues are capable of synthesizing complement components locally, the importance of such local synthesis in immune disease has been difficult to establish
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