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Chapter 17 : Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function
Authors:
Charles N. Serhan1,
Julio Aliberti2
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Affiliations:
1: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115;
2: Divisions of Molecular Immunology and Pulmonary Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229
Content Type: Monograph
Publication Year:
2009
Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
Book DOI:
10.1128/9781555816650
Chapter DOI:
10.1128/9781555816650.ch17
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Abstract:
Several novel enzymatic pathways were recently identified that are activated during the resolution phase and initiated from precursors eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The protectin family name signifies their formation, potent anti-inflammatory, as well as protective actions demonstrated for the novel and potent DHA-derived 10,17-docasatriene in animal models of stroke and Alzheimer’s disease. Both families, the resolvins and protectins, are potent local-acting agonists of endogenous anti-inflammation and promote resolution-specific processes. The connection(s) of these new lipid mediators to the control of an acute inflammation and its timely resolution are illustrated in this chapter. The chapter focuses on biosynthesis of proresolving mediators via cyclooxygenases and lipoxygenases. COX-2 also plays a key role in the biosynthesis of PGD2, which is a precursor to the cyclopentenones. Precursors are transformed via enzymatic mechanisms to bioactive compounds such as lipoxins, resolvins, and protectins that regulate the duration and magnitude of inflammation. The most likely human cell types and pathways that biosynthesize the bioactive mediators within the resolving exudates were reconstructed in vitro, which involved cell-cell interactions in vivo within the exudates. Emerging evidence indicates that the immunomodulatory actions of several lipid mediators are exploited by pathogens, including fungi and helminths. In such cases, it seems that modulation of immunity by suppressing host proinflammatory responses is the aim. The interplay between these mediators, the induction of 5-LO, and the control of immune responses in vivo await further investigation.
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
Figures
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function
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Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
/content/10.1128/9781555816650.ch17.ch17fig01
FIGURE 1
Lipid mediators during the initiation and resolution of acute inflammation.
10.1128/9781555816650/f0268-01_thmb.gif
10.1128/9781555816650/f0268-01.gif
FIGURE 1
Lipid mediators during the initiation and resolution of acute inflammation.
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
/content/10.1128/9781555816650.ch17.ch17fig02
FIGURE 2
Eicosanoids and their proinflammatory and proresolution actions.
10.1128/9781555816650/f0270-01_thmb.gif
10.1128/9781555816650/f0270-01.gif
FIGURE 2
Eicosanoids and their proinflammatory and proresolution actions.
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
/content/10.1128/9781555816650.ch17.ch17fig03
FIGURE 3
Biosynthesis of E-series resolvins.
10.1128/9781555816650/f0273-01_thmb.gif
10.1128/9781555816650/f0273-01.gif
FIGURE 3
Biosynthesis of E-series resolvins.
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
/content/10.1128/9781555816650.ch17.ch17fig04
FIGURE 4
Biosynthesis of D-series resolvins.
10.1128/9781555816650/f0274-01_thmb.gif
10.1128/9781555816650/f0274-01.gif
FIGURE 4
Biosynthesis of D-series resolvins.
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
/content/10.1128/9781555816650.ch17.ch17fig05
FIGURE 5
Protectin D1/neuro-protectin D1 biosynthesis and related dihydroxydocosatrienes.
10.1128/9781555816650/f0275-01_thmb.gif
10.1128/9781555816650/f0275-01.gif
FIGURE 5
Protectin D1/neuro-protectin D1 biosynthesis and related dihydroxydocosatrienes.
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
/content/10.1128/9781555816650.ch17.ch17fig06
FIGURE 6
Leukocyte- and pathogen-mediated synthesis of lipoxins.
10.1128/9781555816650/f0276-01_thmb.gif
10.1128/9781555816650/f0276-01.gif
FIGURE 6
Leukocyte- and pathogen-mediated synthesis of lipoxins.
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
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Tables
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function
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Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
/content/10.1128/9781555816650.ch17.ch17tab01
TABLE 1
Lipoxins reduce inflammation and promote resolution
TABLE 1
Lipoxins reduce inflammation and promote resolution
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
/content/10.1128/9781555816650.ch17.ch17tab02
TABLE 2
Lipoxin deficiencies in human disease and proresolving actions after lipoxin analog treatment in animal disease models
TABLE 2
Lipoxin deficiencies in human disease and proresolving actions after lipoxin analog treatment in animal disease models
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
/content/10.1128/9781555816650.ch17.ch17tab03
TABLE 3
Resolvins in models of human diseases
TABLE 3
Resolvins in models of human diseases
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17
/content/10.1128/9781555816650.ch17.ch17tab04
TABLE 4
Protectins in models of human diseases
TABLE 4
Protectins in models of human diseases
Citation:
Serhan C, Aliberti J.
2009.
Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function,
p 267-280.
In
Russell D, Gordon S (ed),
Phagocyte-Pathogen Interactions.
ASM Press, Washington, DC.
doi: 10.1128/9781555816650.ch17