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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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Immunohistochemical localization of C3 in WT background chimeric mice treated with HSA/LPS.100× views of kidney sections from WTIR/WT (a) and WTIR/C3KO (b) chimeras stained with FITC-conjugated goat anti-mouse C3c.
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pone-0003334-g004: Immunohistochemical localization of C3 in WT background chimeric mice treated with HSA/LPS.100× views of kidney sections from WTIR/WT (a) and WTIR/C3KO (b) chimeras stained with FITC-conjugated goat anti-mouse C3c.

Mentions: All animals receiving HSA/LPS injections developed a proliferative glomerulonephritis (HSA/LPS treated mice are shown in Figure 2c–f) as compared to a WT and C3KO mouse treated with saline shown in Figure 2a–b. FITC-conjugated anti-CD14 staining demonstrated that the predominate cell type infiltrating the glomeruli was monocytes (Figure 3c–f). Background staining of CD14 in either a WT or a 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). As objective measures of the severity of glomerular inflammation, glomerular cell counts and crescent formation were determined for each animal, and among group comparisons made. There were no differences in either measure of nephritic severity among the chimera groups (Table 2).


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

Welch TR, Blystone LW - PLoS ONE (2008)

Immunohistochemical localization of C3 in WT background chimeric mice treated with HSA/LPS.100× views of kidney sections from WTIR/WT (a) and WTIR/C3KO (b) chimeras stained with FITC-conjugated goat anti-mouse C3c.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553262&req=5

pone-0003334-g004: Immunohistochemical localization of C3 in WT background chimeric mice treated with HSA/LPS.100× views of kidney sections from WTIR/WT (a) and WTIR/C3KO (b) chimeras stained with FITC-conjugated goat anti-mouse C3c.
Mentions: All animals receiving HSA/LPS injections developed a proliferative glomerulonephritis (HSA/LPS treated mice are shown in Figure 2c–f) as compared to a WT and C3KO mouse treated with saline shown in Figure 2a–b. FITC-conjugated anti-CD14 staining demonstrated that the predominate cell type infiltrating the glomeruli was monocytes (Figure 3c–f). Background staining of CD14 in either a WT or a 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). As objective measures of the severity of glomerular inflammation, glomerular cell counts and crescent formation were determined for each animal, and among group comparisons made. There were no differences in either measure of nephritic severity among the chimera groups (Table 2).

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