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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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Related in: MedlinePlus

Confirmation of hematologic reconstitution of mice that were lethally irradiated and then transplanted with donor bone marrow cells; magnification, ×100.a: Wright-Giemsa stained peripheral blood smear from a C3KO animal 14 weeks after bone marrow transplant from a WT mouse. Note presence of all three cell lines (erythrocytes, leukocytes, platelets). b: Hematoxylin and eosin stained spleen section from a C3KO mouse 14 weeks after transplantation from a WT animal. Note normal appearing lymphatic nodules.
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pone-0003334-g001: Confirmation of hematologic reconstitution of mice that were lethally irradiated and then transplanted with donor bone marrow cells; magnification, ×100.a: Wright-Giemsa stained peripheral blood smear from a C3KO animal 14 weeks after bone marrow transplant from a WT mouse. Note presence of all three cell lines (erythrocytes, leukocytes, platelets). b: Hematoxylin and eosin stained spleen section from a C3KO mouse 14 weeks after transplantation from a WT animal. Note normal appearing lymphatic nodules.

Mentions: The bone marrow transplantation process created chimeras that survived to undergo the injection protocol. Examination of peripheral blood smears and reticuloendothelial structures (spleen) of selected animals confirmed hematologic reconstitution (Figure 1).


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

Welch TR, Blystone LW - PLoS ONE (2008)

Confirmation of hematologic reconstitution of mice that were lethally irradiated and then transplanted with donor bone marrow cells; magnification, ×100.a: Wright-Giemsa stained peripheral blood smear from a C3KO animal 14 weeks after bone marrow transplant from a WT mouse. Note presence of all three cell lines (erythrocytes, leukocytes, platelets). b: Hematoxylin and eosin stained spleen section from a C3KO mouse 14 weeks after transplantation from a WT animal. Note normal appearing lymphatic nodules.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003334-g001: Confirmation of hematologic reconstitution of mice that were lethally irradiated and then transplanted with donor bone marrow cells; magnification, ×100.a: Wright-Giemsa stained peripheral blood smear from a C3KO animal 14 weeks after bone marrow transplant from a WT mouse. Note presence of all three cell lines (erythrocytes, leukocytes, platelets). b: Hematoxylin and eosin stained spleen section from a C3KO mouse 14 weeks after transplantation from a WT animal. Note normal appearing lymphatic nodules.
Mentions: The bone marrow transplantation process created chimeras that survived to undergo the injection protocol. Examination of peripheral blood smears and reticuloendothelial structures (spleen) of selected animals confirmed hematologic reconstitution (Figure 1).

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