Chapter 21 : Lipids

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Lipids are an essential constituent of cell membranes and are sources of energy. Lipid mediator generation can be entirely innate or composite via an adaptive immune step. This chapter addresses only primary innate or exogenous signals assessed in vitro and in vivo. In vivo discussion is limited to studies in null mouse strains for clarity. The activation of phospholipase A (PLA) with release of arachidonic acid provides the substrate for all eicosanoids, namely, prostanoids and leukotrienes (LTs). Although certain residual lysophospholipids by acetylation become platelet-activating factor (PAF), other lysophospholipids are generated by more complex pathways. PLA comprises a diverse family of enzymes that cleave the -2 position of glycerophospholipids to form a fatty acid and a lysophospolipid. PLA is involved in the digestion of phospholipids in the diet and in the metabolism and turnover of phospholipids in cell membranes. Lysophosphatidic acid (LPA) and S1P are bioactive lysophospholipids with cell functions that include growth, inhibition of apoptosis, differentiation, migration, and cytoskeletal rearrangement. The major biosynthetic pathway of LPA is initiated by the action of phospholipase D on phospholipids to form phosphatidic acid and then the cleavage of the -2 position of the fatty acid by phosphatidic acid-specific PLA to form LPA. Two lysophospholipds containing lysophosphorylcholine, namely, sphingosylphosphorylcholine (SPC) and lysophosphatidylcholine (LPC), are involved in many biological processes including cell proliferation and growth inhibition.

Citation: Austen K, Kanaoka Y. 2004. Lipids, p 417-432. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch21
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Image of FIGURE 1

Biosynthetic pathway of prostanoids and thromboxanes. cPLA, cytosolic phospholipase A; PGHS, prostaglandin endoperoxide synthase; PGDS, prostaglandin D synthase; PGES, prostaglandin E synthase; PGFS, prostaglandin F synthase; PGIS, prostacyclin synthase; TXS, thromboxane synthase.

Citation: Austen K, Kanaoka Y. 2004. Lipids, p 417-432. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch21
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Image of FIGURE 2

Biosynthetic pathway of leukotrienes. 5-LO, 5-lipoxygenase; FLAP, 5-LO activating protein; 5-HPETE, 5-hydroperoxyeicosatetraenoic acid; LT, leukotriene; LTAH, LTA hydrolase; LTCS, LTC synthase; γ-GT, γ-glutamyl transpeptidase; γ-GL, γ-glutamyl leukotrienase; DiP, dipeptidase.

Citation: Austen K, Kanaoka Y. 2004. Lipids, p 417-432. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch21
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Innate immune responses in mice lacking eicosanoid synthetic enzymes and receptors

Citation: Austen K, Kanaoka Y. 2004. Lipids, p 417-432. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch21

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