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Environmental influences on fatty acid composition of membranes from autoimmune MRL lpr/lpr mice
K V Hackshaw1, S L Kunesh, N A Jackson
1Department of Internal Medicine, William H. Davis Medical Research Center, Ohio State University, Columbus 43210, USA.
Abstract:
We analyzed fatty acid make up of cells and organs from autoimmune and immunologically normal mice to determine whether intrinsic differences in composition might be associated with an inflammatory phenotype. Macrophages (MO) isolated from 4-6-week-old MRL lpr/lpr mice were cultured with phorbol ester (PMA), fibroblast growth factor-1 (FGF-1), fibroblast growth factor-2 (FGF-2) and medium control to determine whether these cell signals might induce membrane fatty acid changes. Individual phospholipid analysis showed 8.4- and 5.1-fold increases in phosphatidylcholine arachidonate (20:4) mole % over baseline values following culture with FGF-1 and FGF-2, respectively. Unfractionated analysis on kidney and liver extracts from 4-6 week MRL lpr/lpr, 16-20 week lpr and 12-20 week MRL +/-/+/- mice demonstrated no significant intrastrain fatty acid differences. Higher levels of 20:4 in 4-6 week lpr mice were noted compared to 16-20 week lpr or +/+ mice in kidney, and liver samples (P < 0.05). It is possible that membrane changes precipitated by microenvironmental cytokine concentrations may contribute to the expression of autoimmune disease in this model.
Insights
Autoimmune mice show altered fatty acid composition in cells and organs. Specifically, fibroblast growth factors (FGFs) increase arachidonate (20:4) levels in macrophages, potentially contributing to inflammatory disease.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Autoimmune diseases are characterized by inflammation.
- Fatty acid composition of cell membranes may influence cellular function and inflammatory responses.
- MRL lpr/lpr mice serve as a model for autoimmune disease.
Purpose of the Study:
- To investigate if intrinsic fatty acid differences in cells and organs are associated with an inflammatory phenotype in autoimmune mice.
- To determine if specific cell signals, like fibroblast growth factors (FGFs), can induce changes in macrophage membrane fatty acid composition.
Main Methods:
- Analysis of fatty acid composition in cells and organs of autoimmune (MRL lpr/lpr) and normal mice.
- Culture of macrophages (MO) from MRL lpr/lpr mice with phorbol ester (PMA), FGF-1, FGF-2, and medium control.
- Phospholipid analysis to quantify changes in fatty acid levels, particularly arachidonate (20:4).
Main Results:
- Fibroblast growth factor-1 (FGF-1) and FGF-2 significantly increased phosphatidylcholine arachidonate (20:4) levels in cultured macrophages.
- No significant intrastrain fatty acid differences were observed in kidney and liver extracts across different ages and strains of mice.
- Younger MRL lpr/lpr mice (4-6 weeks) exhibited higher levels of 20:4 in kidney and liver compared to older MRL lpr/lpr or normal mice.
Conclusions:
- Cellular membrane fatty acid alterations, specifically increased arachidonate (20:4), may occur in response to microenvironmental signals like FGFs.
- These membrane changes could potentially contribute to the development or exacerbation of autoimmune disease in susceptible individuals.
- Further research is needed to elucidate the precise mechanisms linking fatty acid metabolism and autoimmune pathogenesis.