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Lipocortins

  • Bernard Rothhut
  • Françoise Russo-Marie
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 245)

Abstract

The various membrane events occuring during the inflammatory reaction and leading to the formation of lipid-derived mediators (prostaglandins, leukotrienes and PAF-acether) always involve a membrane enzyme activation namely phospholipase A2. This activation leads to the cleavage of the phospholipids present in the membrane and permits the release of an unsaturated fatty acid from the 2 position - usually, arachidonic acid - and to the simultaneous formation of a lysophospholipid. If the phospholipase A2-target phospholipid is an ether phosphatidyl choline, the lyso derivative formed is lyso PAF, the precursor of PAF-acether (Platelet Activating Factor, 1-0- alkyl- 2 - acetyl - sn- glycero- 3 - phosphocholine) (Figure 1). In inflammatory cells, the signal induced by inflammatory stimuli is transduced by a succession of events leading to the phospholipase A2 stimulation, allowing consequently the release in the cell of either arachidonic acid, precursor of prostaglandins and leukotrienes, or lyso-PAF, precursor of PAF-acether. These products, once formed, leave the cell and are able to stimulate neighbouring cell membranes, inducing again phospholipase A2 stimulation through stimulus-coupling events. An oversimplified view of the inflammatory reaction can be presented as an event stimulating the membrane of inflammatory cells, event coupled to transducing systems allowing the formation of lipid-derived mediators. These mediators, being stimuli by themselves amplify the phenomenon, rendering the inflammatory reaction rather similar to a nuclear reaction where the pile is phospholipase A2, and the combustible, phospholipids, always renewed by powerful acylating systems. Would phospholipase A2 be alone, the reaction would be endless and could become harmful for the biological environment where it takes place. Consequently, there must be some naturally occuring biological systems capable of controlling such a reaction. The discovery of lipocortin, a natural endogenous phospholipase A2 inhibitor, has focused the attention on the central role of pnospholipase A2 in the inflammatory reaction. Indeed, this discovery has been linked to the knowledge of the biochemical and cellular mode of action of glucocorticosteroids, which inhibit phospholipase A2 activity through the induction of the synthesis of lipocortin (Figure 2).

Keywords

Inositol Triphosphate Epidermal Growth Factor Receptor Kinase Murine Thymocyte Tyrosine Kinase Substrate Rabbit Neutrophil 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Bernard Rothhut
    • 1
  • Françoise Russo-Marie
    • 1
  1. 1.Unité des VeninsUnité Associée Institut Pasteur / INSERM N0 285Paris Cedex 15France

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