Lipids, derived from either endogenous or exogenous sources, affect many cell signalling pathways via a variety of mechanisms. Many of the established cell signalling molecules are generated directly from membrane phospholipids (e.g. inositol-1,4,5-trisphosphate, diacylglycerol, phosphatidic acid, choline, ceramide, platelet-activating factor, arachidonic acid). These have important roles in regulating the activity of proteins involved in immune-cell responses.
The concentration and/or composition of lipid-derived signalling molecules have been shown to be sensitive to n-3 PUFA availability either in cell culture (Jenski et al., 1995) or through the diet (Huang et al., 1992; Fowler et al., 1993; Sperling et al., 1993; Marignani and Sebaldt, 1995; Jolly et al., 1997; Sanderson and Calder, 1998b). This may be due to either altered activity of the enzymes that generate the signals or to altered composition of the substrate molecules. There is evidence to support each of these possibilities (see Miles and Calder, 1998). For example, lymphocyte phospholipase C7 activity is reduced after feeding a diet rich in fish oil, which might account for the decreased generation of signalling molecules observed (Sanderson and Calder, 1998b). There is also evidence that arachidonic acid released from the plasma membrane has a direct role in regulating some immune-cell functions, such as natural killer cell granule release and cell-mediated toxicity (Cifone et al., 1993). In addition, arachidonic acid is an intracellular activator of the nicotinamide adenine dinu-cleotide phosphate (NADPH) oxidase enzyme in neutrophils (Sakata et al., 1987), and enrichment of arachidonic acid in neutrophil membranes is reported to increase the oxidative burst of neutrophils (Badwey et al., 1981, 1984; Hardy et al., 1991). Dietary lipids have been demonstrated to influence the pattern of fatty acids released from lymphocytes (Sanderson et al., 2000).
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