Polyunsaturated fatty acids and membrane organization: elucidating mechanisms to balance immunotherapy and susceptibility to infection - PubMed (original) (raw)

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Polyunsaturated fatty acids and membrane organization: elucidating mechanisms to balance immunotherapy and susceptibility to infection

Saame Raza Shaikh et al. Chem Phys Lipids. 2008 May.

Abstract

Polyunsaturated fatty acids (PUFAs), notably of the n-3 series, have immunosuppressive effects which make these molecules candidates for treating inflammatory symptoms associated with cardiovascular disease, obesity, arthritis, and asthma. However, immunosuppression by PUFAs could increase susceptibility to bacterial and viral infection. A detailed molecular picture is required in order to understand the balance between the benefits and risks of utilizing PUFAs as adjuvant immunosuppressants. Here we review evidence that incorporation of PUFAs into membrane lipids of antigen presenting cells (APCs) downregulates APC function. We propose that PUFAs modulate antigen presentation by altering the organization of lipid and protein molecules of the plasma membrane and endomembranes; this alters recognition and responses by T cells. The foundation of our hypothesis is built on data from artificial bilayer experiments which provide the physical principles by which PUFA acyl chains affect membrane architecture. This review also reconciles conflicting results in the literature by discussing the advantages and disadvantages of differing methods of PUFA treatment of cells. We suggest that membrane modulation of immune cells may be an important and overlooked mechanism of immunomodulation. In addition, we propose that mechanistic studies with defined experimental protocols will speed the translation of laboratory studies on PUFAs to the clinic.

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Figures

Figure 1

Figure 1

The method of lipid delivery influences MHC class I surface expression levels. (Top) Modifcation of membrane structure with AA- and DHA-containing heteroacid PCs in the presence of the plasma membrane expander PVP for 2 hours increases MHC class I surface levels of human B lymphoblasts. Modification with the same heteroacid PC SUVs has no effect on MHC class I expression. (Bottom) Feeding human B lymphoblasts 100 µM AA and DHA complexed to fatty acid-free BSA for 12 hours in serum-free conditions lowers MHC class I surface levels whereas no effects are observed in the presence of serum. Surface expression levels of MHC class I were obtained and quantified with FACS analysis of Ke2-Cy5 antibody binding to HLA-A2 and –B7 alleles.

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