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Immune complex glomerulonephritis following bone marrow transplantation in C3 deficient mice.

Welch TR, Blystone LW - PLoS ONE (2008)

Bottom Line: All HSA/LPS animals developed a proliferative GN with glomerular infiltration by monocytes.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.In this model of GN, local synthesis of C3 by infiltrating cells does not appear to be of pathologic importance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, SUNY Upstate Medical University, Syracuse, New York, United States of America. welcht@upstate.edu

ABSTRACT

Background: The 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 findings: We 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/significance: In this model of GN, local synthesis of C3 by infiltrating cells does not appear to be of pathologic importance.

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Plasma C3 concentrations as determined by ELISA.Measurements are from terminal plasma samples and demonstrate normal levels of C3 in all WT mice. C3KO animals and C3KOIR/C3KO chimeras had C3 concentrations below 0.001 mg/ml, approaching the lower limit of the assay. However, there was measurable C3 in the plasma of C3KOIR/WT chimeric mice.
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pone-0003334-g005: Plasma C3 concentrations as determined by ELISA.Measurements are from terminal plasma samples and demonstrate normal levels of C3 in all WT mice. C3KO animals and C3KOIR/C3KO chimeras had C3 concentrations below 0.001 mg/ml, approaching the lower limit of the assay. However, there was measurable C3 in the plasma of C3KOIR/WT chimeric mice.

Mentions: Plasma C3 concentrations in the experimental animals are shown in Figure 5. There were no significant differences in concentration between the chimeras with WT backgrounds (WTIR/C3KO and WTIR/WT). On the other hand, when C3KO animals were reconstituted with WT bone marrow cells, detectable C3 was present in plasma, albeit at only a fraction (0.67%) of that found in WT animals. C3KO animals and C3KOIR/C3KO chimeras had C3 concentrations below 0.001 mg/ml, approaching the lower limit of the assay.


Immune complex glomerulonephritis following bone marrow transplantation in C3 deficient mice.

Welch TR, Blystone LW - PLoS ONE (2008)

Plasma C3 concentrations as determined by ELISA.Measurements are from terminal plasma samples and demonstrate normal levels of C3 in all WT mice. C3KO animals and C3KOIR/C3KO chimeras had C3 concentrations below 0.001 mg/ml, approaching the lower limit of the assay. However, there was measurable C3 in the plasma of C3KOIR/WT chimeric mice.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2553262&req=5

pone-0003334-g005: Plasma C3 concentrations as determined by ELISA.Measurements are from terminal plasma samples and demonstrate normal levels of C3 in all WT mice. C3KO animals and C3KOIR/C3KO chimeras had C3 concentrations below 0.001 mg/ml, approaching the lower limit of the assay. However, there was measurable C3 in the plasma of C3KOIR/WT chimeric mice.
Mentions: Plasma C3 concentrations in the experimental animals are shown in Figure 5. There were no significant differences in concentration between the chimeras with WT backgrounds (WTIR/C3KO and WTIR/WT). On the other hand, when C3KO animals were reconstituted with WT bone marrow cells, detectable C3 was present in plasma, albeit at only a fraction (0.67%) of that found in WT animals. C3KO animals and C3KOIR/C3KO chimeras had C3 concentrations below 0.001 mg/ml, approaching the lower limit of the assay.

Bottom Line: All HSA/LPS animals developed a proliferative GN with glomerular infiltration by monocytes.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.In this model of GN, local synthesis of C3 by infiltrating cells does not appear to be of pathologic importance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, SUNY Upstate Medical University, Syracuse, New York, United States of America. welcht@upstate.edu

ABSTRACT

Background: The 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 findings: We 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/significance: In this model of GN, local synthesis of C3 by infiltrating cells does not appear to be of pathologic importance.

Show MeSH
Related in: MedlinePlus