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12 - Lipid Mediators in Acute Inflammation and Resolution: Eicosanoids, PAF, Resolvins, and Protectins

from PART III - CHEMICAL MEDIATORS

Published online by Cambridge University Press:  05 April 2014

By
Charles N. Serhan  and
Jesper Z. Haeggström
Edited by
Charles N. Serhan ,
Peter A. Ward  and
Derek W. Gilroy
With contributions by
Samir S. Ayoub
Charles N. Serhan
Affiliation:
Brigham and Women's Hospital
Jesper Z. Haeggström
Affiliation:
Karolinska Institute
Charles N. Serhan
Affiliation:
Harvard Medical School
Peter A. Ward
Affiliation:
University of Michigan, Ann Arbor
Derek W. Gilroy
Affiliation:
University College London
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Summary

INTRODUCTION

Autacoids are locally acting substances that are rapidly biosynthesized in response to specific stimuli, act quickly, and are usually deactivated by metabolism. Eicosanoids are a chemically diverse family of arachidonic acid–derived autacoids that have critical roles in cardiovascular, inflammatory, and reproductive physiology. Pharmacologic interventions in eicosanoid pathways – including the nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, and leukotriene inhibitors – are useful in the clinical management of inflammation, pain, and fever. Given the many important bioactivities of lipid mediator eicosanoids, resolvins, and protectins, future research may lead to the development of new therapeutics for the treatment of inflammatory conditions, autoimmune diseases, asthma, glomerulonephritis, cancer, sleep disorders, and Alzheimer's disease.

BIOSYNTHESIS OF EICOSANOIDS

Eicosanoids are crucially involved in a number of metabolic pathways that have diverse roles in inflammation and cellular signaling. These pathways center on reactions involving the metabolism of arachidonic acid (Figure 12.1). The following considers the biochemical steps leading to arachidonic acid synthesis, then discusses the cyclooxygenase (COX), lipoxygenase (LOX), epoxygenase, and isoprostane pathways of arachidonic acid metabolism. Arachidonic acid (cis-, cis-, cis-, cis-5, 8, 11, 14-eicosatetraenoic acid), the common precursor to eicosanoids, must be synthesized from the essential fatty acid precursor linoleic acid (cis, cis-9, 12-octadecadienoic acid), which can be obtained only from dietary sources. In cells, arachidonic acid is esterified to the sn 2 position of the membrane phospholipids predominantly in phosphatidylcholine phosphatidylethanolamine, and phosphatidyl inositol.

Type
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Information
Fundamentals of Inflammation , pp. 153 - 174
Publisher: Cambridge University Press
Print publication year: 2010

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References

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