Resolvin E2 formation and impact in inflammation resolution

Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized proresolving mediators derived from polyunsaturated fatty acids are of interest. In this study, we report that resolvin E2 (RvE2) from eicosapentaenoic acid is endogenous...

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Published inThe Journal of immunology (1950) Vol. 188; no. 9; pp. 4527 - 4534
Main Authors Oh, Sungwhan F, Dona, Maria, Fredman, Gabrielle, Krishnamoorthy, Sriram, Irimia, Daniel, Serhan, Charles N
Format Journal Article
LanguageEnglish
Published United States 01.05.2012
Subjects
Animals
Chemotaxis - drug effects
Chemotaxis - immunology
Down-Regulation - drug effects
Down-Regulation - immunology
Eicosapentaenoic Acid - analogs & derivatives
Eicosapentaenoic Acid - blood
Eicosapentaenoic Acid - immunology
Eicosapentaenoic Acid - pharmacology
Female
Humans
Immunity, Innate
Inflammation - blood
Inflammation - immunology
Inflammation - pathology
Integrins - biosynthesis
Integrins - immunology
Male
Mice
Neutrophils - immunology
Neutrophils - metabolism
Neutrophils - pathology
Phagocytosis - drug effects
Phagocytosis - immunology
Platelet Activating Factor - immunology
Platelet Activating Factor - metabolism
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Abstract Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized proresolving mediators derived from polyunsaturated fatty acids are of interest. In this study, we report that resolvin E2 (RvE2) from eicosapentaenoic acid is endogenously produced during self-limited murine peritonitis in both the initiation and resolution phases. RvE2 (1-10 nM) carries potent leukocyte-directed actions that include: 1) regulating chemotaxis of human neutrophils; and 2) enhancing phagocytosis and anti-inflammatory cytokine production. These actions appear to be mediated by leukocyte G-protein-coupled receptors as preparation of labeled RvE2 gave direct evidence for specific binding of radiolabeled RvE2 to neutrophils (K(d) 24.7 ± 10.1 nM) and resolvin E1 activation of recombinant G-protein-coupled receptors was assessed. In addition to the murine inflammatory milieu, RvE2 was also identified in plasma from healthy human subjects. RvE2 rapidly downregulated surface expression of human leukocyte integrins in whole blood and dampened responses to platelet-activating factor. Together, these results indicate that RvE2 can stimulate host-protective actions throughout initiation and resolution in the innate inflammatory responses.
AbstractList Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized proresolving mediators derived from polyunsaturated fatty acids are of interest. In this study, we report that resolvin E2 (RvE2) from eicosapentaenoic acid is endogenously produced during self-limited murine peritonitis in both the initiation and resolution phases. RvE2 (1–10 nM) carries potent leukocyte-directed actions that include: 1) regulating chemotaxis of human neutrophils; and 2) enhancing phagocytosis and anti-inflammatory cytokine production. These actions appear to be mediated by leukocyte G-protein–coupled receptors as preparation of labeled RvE2 gave direct evidence for specific binding of radiolabeled RvE2 to neutrophils (Kd 24.7 ± 10.1 nM) and resolvin E1 activation of recombinant G-protein–coupled receptors was assessed. In addition to the murine inflammatory milieu, RvE2 was also identified in plasma from healthy human subjects. RvE2 rapidly downregulated surface expression of human leukocyte integrins in whole blood and dampened responses to platelet-activating factor. Together, these results indicate that RvE2 can stimulate host-protective actions throughout initiation and resolution in the innate inflammatory responses.
Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized proresolving mediators derived from polyunsaturated fatty acids are of interest. In this study, we report that resolvin E2 (RvE2) from eicosapentaenoic acid is endogenously produced during self-limited murine peritonitis in both the initiation and resolution phases. RvE2 (1-10 nM) carries potent leukocyte-directed actions that include: 1) regulating chemotaxis of human neutrophils; and 2) enhancing phagocytosis and anti-inflammatory cytokine production. These actions appear to be mediated by leukocyte G-protein-coupled receptors as preparation of labeled RvE2 gave direct evidence for specific binding of radiolabeled RvE2 to neutrophils (K(d) 24.7 ± 10.1 nM) and resolvin E1 activation of recombinant G-protein-coupled receptors was assessed. In addition to the murine inflammatory milieu, RvE2 was also identified in plasma from healthy human subjects. RvE2 rapidly downregulated surface expression of human leukocyte integrins in whole blood and dampened responses to platelet-activating factor. Together, these results indicate that RvE2 can stimulate host-protective actions throughout initiation and resolution in the innate inflammatory responses.
Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized proresolving mediators derived from polyunsaturated fatty acids are of interest. In this study, we report that resolvin E2 (RvE2) from eicosapentaenoic acid is endogenously produced during self-limited murine peritonitis in both the initiation and resolution phases. RvE2 (1-10 nM) carries potent leukocyte-directed actions that include: 1) regulating chemotaxis of human neutrophils; and 2) enhancing phagocytosis and anti-inflammatory cytokine production. These actions appear to be mediated by leukocyte G-protein-coupled receptors as preparation of labeled RvE2 gave direct evidence for specific binding of radiolabeled RvE2 to neutrophils (Kd 24.7 plus or minus 10.1 nM) and resolvin E1 activation of recombinant G-protein-coupled receptors was assessed. In addition to the murine inflammatory milieu, RvE2 was also identified in plasma from healthy human subjects. RvE2 rapidly downregulated surface expression of human leukocyte integrins in whole blood and dampened responses to platelet-activating factor. Together, these results indicate that RvE2 can stimulate host-protective actions throughout initiation and resolution in the innate inflammatory responses.
Author Oh, Sungwhan F
Irimia, Daniel
Fredman, Gabrielle
Krishnamoorthy, Sriram
Dona, Maria
Serhan, Charles N
Author_xml – sequence: 1
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– sequence: 2
  givenname: Maria
  surname: Dona
  fullname: Dona, Maria
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  fullname: Fredman, Gabrielle
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  surname: Krishnamoorthy
  fullname: Krishnamoorthy, Sriram
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  surname: Irimia
  fullname: Irimia, Daniel
– sequence: 6
  givenname: Charles N
  surname: Serhan
  fullname: Serhan, Charles N
BackLink https://www.ncbi.nlm.nih.gov/pubmed/22450811$$D View this record in MEDLINE/PubMed
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Snippet Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized proresolving mediators...
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pubmed
SourceType Aggregation Database
Index Database
StartPage 4527
SubjectTerms Animals
Chemotaxis - drug effects
Chemotaxis - immunology
Down-Regulation - drug effects
Down-Regulation - immunology
Eicosapentaenoic Acid - analogs & derivatives
Eicosapentaenoic Acid - blood
Eicosapentaenoic Acid - immunology
Eicosapentaenoic Acid - pharmacology
Female
Humans
Immunity, Innate
Inflammation - blood
Inflammation - immunology
Inflammation - pathology
Integrins - biosynthesis
Integrins - immunology
Male
Mice
Neutrophils - immunology
Neutrophils - metabolism
Neutrophils - pathology
Phagocytosis - drug effects
Phagocytosis - immunology
Platelet Activating Factor - immunology
Platelet Activating Factor - metabolism
Title Resolvin E2 formation and impact in inflammation resolution
URI https://www.ncbi.nlm.nih.gov/pubmed/22450811
https://search.proquest.com/docview/1014108069
Volume 188
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