Lipid Rafts & Co.: An integrated model of membrane organization in T cell activation

ArticleinProgress in Lipid Research 45(3):187-202 · June 2006with2 Reads
DOI: 10.1016/j.plipres.2006.01.002 · Source: PubMed
The model of membrane compartmentalization by self-organizing functional lipid microdomains, named lipid rafts, has been a fruitful concept resulting in great progress in understanding T cell signal transduction. However, due to recent results it has become clear that lipid rafts describe only one out of several membrane organizing principles crucial for T cell activation besides fences and pickets and protein-protein interactions that take part in the formation of the immunological synapse as a highly organized structure at the T cell contact site to the antigen-presenting cell. This review describes the concepts of lipid rafts and other membrane organizing principles to evolve a novel integrated model on the functional role of microdomains in immunological synapse formation and T cell activation. Further research has to elucidate the relative contribution and interrelation of different modes of membrane organization in productive T cell activation.
    • "EPA interrupts immune cell responses through alterations in lipid rafts. Both in vitro and in vivo studies demonstrated how n-3 fatty acids disrupt the lipid rafts, thereby altering the immune cell signaling mechanism in these cells203204205206207208 (Fig. 8 ). A report by Gurzell et al. suggested that DHA enhanced the B-cell immune responses against infection and helped in clearing pathogens by producing antibodies and dampening inflammation, both ex vivo and in vivo using a SMAD −/− colitis-prone mouse model [209]. "
    [Show abstract] [Hide abstract] ABSTRACT: Epidemiological and laboratory data support the protective effects of bioactive nutrients in our diets for various diseases. Along with various factors, such as genetic history, alcohol, smoking, exercise, and dietary choices play a vital role in affecting an individual's immune responses towards a transforming cell, by either preventing or accelerating a neoplastic transformation. Ample evidence suggests that dietary nutrients control the inflammatory and pro-tumorigenic responses in immune cells. Immunoprevention is usually associated with the modulation of immune responses that help in resolving the inflammation, thus improving clinical outcome. Various metabolic pathway-related nutrients, including glutamine, arginine, vitamins, minerals, and long-chain fatty acids, are important components of immunonutrient mixes. Epidemiological studies related to these substances have reported different results, with no or minimal effects. However, several studies suggest that these nutrients may have immune-modulating effects that may lower cancer risk. Preclinical studies submit that most of these components may provide beneficial effects. The present review discusses the available data, the immune-modulating functions of these nutrients, and how these substances could be used to study immune modulation in a neoplastic environment. Further research will help to determine whether the mechanistic signaling pathways in immune cells altered by nutrients can be exploited for cancer prevention and treatment. This article is protected by copyright. All rights reserved.
    Full-text · Article · Feb 2016
    • "Zeyda et al. [37] also showed enriching cell culture medium with EPA led to the displacement from lipid rafts of LAT (linker for activation of T cells), thus inhibiting T cell signaling. Accordingly, several experimental studies have highlighted the role of lipid rafts in mediating immunosuppression induced by marine n−3 PUFA subsequent to their membrane incorporation into immune cells [30,43]. Indeed, fish oil displaces key signaling proteins from putative lipid rafts, increases the clustering of proteins in cholesterol-dependent microdomains and downregulates signaling pathways. "
    [Show abstract] [Hide abstract] ABSTRACT: Critical illness is a life-threatening multisystem process that can result in significant morbidity and mortality. In most patients, critical illness is preceded by a physiological deterioration, characterized by a catabolic state and intense metabolic changes, resulting in malnutrition and impaired immune functions. In this context, parenteral lipid emulsions may modulate inflammatory and immune reactions, depending on their fatty acid composition. These effects appear to be based on complex modifications in the composition and structure of cell membranes, through eicosanoid and cytokine synthesis and by modulation of gene expression. The pathophysiological mechanisms underlying these fatty acid-induced immune function alterations in critical ill patients are however complex and partially understood. Indeed, despite a very abundant literature, experimental and clinical data remain contradictory. The optimization of lipid emulsion composition thus represents a major challenge for clinical medicine, to adequately modulate the inflammatory pathways. In the present review, we first address the metabolic response to aggression, the effects of parenteral lipid emulsions on inflammation and immunity, and finally the controversial place of these lipid emulsions during critical illness. The analysis furthermore highlights the pathophysiological mechanisms underlying the differential effects of lipid emulsions and their potential for improving the handling of critically ill patients.
    Article · Sep 2015
    • "Furthermore, the activities of the Δ6 and Δ5-desaturase and the activity of the cyclooxygenase are inhibited by both n-3 and n-6 PUFA [37]. Through this mechanism, high intake of PUFA could reduce inflammatory mediators through modulating inflammatory gene expression in immune cells [38]. PUFA may also modulate cytokine production or the release of the soluble TNF receptors through eicosanoid-independent pathways, for example, by influencing membrane composition and fluidity, affecting signal transduction processes or second messenger molecules, or binding to or affecting nuclear receptors such as the peroxisome proliferator receptors or nuclear factor-kB [29,39]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Polyunsaturated fatty acid (PUFA) intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, the relationship between the PUFA and inflammatory factors in the healthy vegetarians were not clear. We aimed to investigate the plasma fatty acids status, and its association with plasma inflammatory factors in Chinese vegetarians and omnivores. Methods A total of 89 male vegetarians and 106 male omnivores were participated the study. Plasma concentrations of inflammatory factors were detected by ELISA, and as standard methods fatty acids were extracted and determined by chromatography. Results Compared with omnivores, vegetarians have significant higher interleukin-6 (IL-6), plasma n-6 PUFA, n-6/n-3, and 18:3n-3; while they have significant lower leukotriene B4 (LTB4), cyclo-oxygenase-2 (COX2) and prostaglandin E2 (PGE2), 20:5n-3, 22:5n-3, 22:6n-3, and n-3 PUFA. In vegetarians, plasma 20:4n-6 was significant positively related to TNF-α. LTB4 was significantly positively related to plasma 22:6n-3, and negatively associated with n-6 PUFA. Conclusion Vegetarians have higher plasma n-6 PUFA and IL-6, but lower LTB4, n-3 PUFA, 22:6n-3, COX2 and PGE2 levels. It would seem appropriate for vegetarians to increase their dietary n-3 PUFA, while reduce dietary n-6 PUFA and thus reduce the risk of chronic inflammatory-related diseases.
    Full-text · Article · Sep 2014
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