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Hepatic and extrahepatic biosynthesis of complement factor C6 in the rat
R B Brauer1, W M Baldwin, D Wang
1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Journal of Immunology (Baltimore, Md. : 1950)
|October 1, 1994
Summary
The liver is the main producer of C6 in rats, but bone marrow cells, specifically myelomonocytes, also contribute significantly to systemic C6 levels. This study clarifies C6 production sources in rats.
Area of Science:
- Immunology
- Hematology
- Transplantation Biology
Background:
- Complement component 6 (C6) is crucial for the formation of the membrane attack complex.
- Understanding the primary sources of C6 is essential for diagnosing and treating complement deficiencies.
Purpose of the Study:
- To delineate the relative contributions of the liver and bone marrow (BM) to systemic C6 production in a rat model.
- To identify the specific cell types within the BM responsible for extrahepatic C6 synthesis.
Main Methods:
- Liver transplantation between C6-sufficient and C6-deficient PVG rats.
- Bone marrow transplantation in irradiated C6-deficient rats, with selective reconstitution of myelomonocyte or lymphoid stem cells.
- Analysis of systemic C6 levels post-transplantation using hemolytic C activity assays.
Main Results:
- Liver grafts restored C6 levels significantly in deficient recipients, confirming the liver as a primary C6 source.
- Bone marrow transplantation from C6-sufficient donors partially restored C6 levels.
- Restoration of C6 activity was observed with BM engraftment enriched in myelomonocytes, but not with lymphoid cell reconstitution.
Conclusions:
- The liver is the principal organ for systemic C6 production in rats.
- Extrahepatic C6 production originates from bone marrow-derived myelomonocytes, not lymphoid cells.
- These findings highlight the complex cellular origins of complement components and their implications for immune function.