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Functional defects of culture-grown bone marrow-derived macrophages from autoimmune MRL/MpJ-lpr/lpr mice
Abstract:
To investigate the primary defects and development of macrophages in MRL/MpJ-/pr/lpr (MRL/l) mice, we used a pure population of macrophages derived from bone marrow precursor cells cultured in the presence of L-cell conditioned medium (LCM) as a source of colony stimulating factor. Bone marrow-derived macrophages (BMM phi) from MRL/l mice had lower antigen presenting activity as detected by the induction of antigen-specific T cell proliferation, than age- and sex-matched control mice (CBA/J). Cell surface antigens (Ia and Mac-1) were determined quantitatively by a cell sorter as markers of macrophage differentiation. The BMM phi from MRL/l contained a much smaller number of Ia antigen-positive macrophages than those from normal mice. Treatment of BMM phi with an Ia-inducing of factor (IFN-gamma) markedly increased the expression of Ia antigens. This increase was significantly greater in BMM phi from MRL/l mice than in BMM phi from control mice. Expression of Mac-1 antigen was not different in BMM phi from the two strains. The Fc-mediated phagocytosis of IgG-coated sheep red blood cells was decreased in BMM phi from MRL/l mice compared with those from control mice. The function of nonspecific phagocytosis as measured by latex-bead incorporation was also impaired in MRL/l mice. The functional defects of MRL/l BMM phi found in these experiments are not secondary defects acquired under the influence of environmental signals during development, but are derived from the primary abnormalities which already exist in myeloid stem cells.
Insights
Macrophages from MRL/l mice exhibit primary functional defects, including reduced antigen presentation and phagocytosis. These impairments stem from intrinsic abnormalities in myeloid stem cells, not environmental factors.
Area of Science:
- Immunology
- Cell Biology
- Autoimmunity
Background:
- MRL/MpJ-/pr/lpr (MRL/l) mice are a model for autoimmune diseases.
- Macrophages play crucial roles in immune responses and antigen presentation.
- Understanding macrophage development and function is key to autoimmune research.
Purpose of the Study:
- To investigate primary defects in macrophage development and function in MRL/l mice.
- To determine if observed macrophage defects are intrinsic or environmentally acquired.
- To compare macrophage characteristics between MRL/l mice and normal control mice (CBA/J).
Main Methods:
- Bone marrow-derived macrophages (BMMφ) were cultured from MRL/l and control mice.
- Antigen-presenting activity was assessed via T cell proliferation assays.
- Cell surface antigens (Ia and Mac-1) were quantified using flow cytometry.
- Phagocytic activity was measured using IgG-coated sheep red blood cells and latex beads.
Main Results:
- MRL/l BMMφ showed significantly lower antigen-presenting activity compared to controls.
- Fewer Ia antigen-positive macrophages were present in MRL/l cultures.
- Interferon-gamma (IFN-γ) treatment induced a greater increase in Ia expression in MRL/l BMMφ.
- Fc-mediated and non-specific phagocytosis were impaired in MRL/l BMMφ.
- Mac-1 antigen expression did not differ between the strains.
Conclusions:
- Functional defects in MRL/l macrophages are primary abnormalities originating in myeloid stem cells.
- These intrinsic defects are not secondary to environmental influences during development.
- The findings provide insights into the cellular basis of autoimmune pathology in MRL/l mice.