Angiotensin-(1-7)/MasR axis promotes migration of monocytes/macrophages with a regulatory phenotype to perform phagocytosis and efferocytosis.
Zaidan, I
Tavares, LP
Sugimoto, MA
Lima, KM
Negreiros-Lima, GL
Teixeira, LC
Miranda, TC
Valiate, BV
Cramer, A
Vago, JP
Campolina-Silva, GH
Souza, JA
Grossi, LC
Pinho, V
Campagnole-Santos, MJ
Santos, RA
Teixeira, MM
Galvão, I
Sousa, LP
- Publisher:
- AMER SOC CLINICAL INVESTIGATION INC
- Publication Type:
- Journal Article
- Citation:
- JCI Insight, 2022, 7, (1), pp. e147819
- Issue Date:
- 2022-01-11
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Zaidan, I | |
dc.contributor.author | Tavares, LP | |
dc.contributor.author | Sugimoto, MA | |
dc.contributor.author | Lima, KM | |
dc.contributor.author | Negreiros-Lima, GL | |
dc.contributor.author | Teixeira, LC | |
dc.contributor.author | Miranda, TC | |
dc.contributor.author | Valiate, BV | |
dc.contributor.author | Cramer, A | |
dc.contributor.author | Vago, JP | |
dc.contributor.author | Campolina-Silva, GH | |
dc.contributor.author | Souza, JA | |
dc.contributor.author | Grossi, LC | |
dc.contributor.author | Pinho, V | |
dc.contributor.author | Campagnole-Santos, MJ | |
dc.contributor.author | Santos, RA | |
dc.contributor.author | Teixeira, MM | |
dc.contributor.author | Galvão, I | |
dc.contributor.author | Sousa, LP | |
dc.date.accessioned | 2023-02-06T03:24:30Z | |
dc.date.available | 2021-11-24 | |
dc.date.available | 2023-02-06T03:24:30Z | |
dc.date.issued | 2022-01-11 | |
dc.identifier.citation | JCI Insight, 2022, 7, (1), pp. e147819 | |
dc.identifier.issn | 2379-3708 | |
dc.identifier.issn | 2379-3708 | |
dc.identifier.uri | http://hdl.handle.net/10453/165933 | |
dc.description.abstract | Nonphlogistic migration of macrophages contributes to the clearance of pathogens and apoptotic cells, a critical step for the resolution of inflammation and return to homeostasis. Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system that acts through Mas receptor (MasR). Ang-(1-7) has recently emerged as a novel proresolving mediator, yet Ang-(1-7) resolution mechanisms are not fully determined. Herein, Ang-(1-7) stimulated migration of human and murine monocytes/macrophages in a MasR-, CCR2-, and MEK/ERK1/2-dependent manner. Pleural injection of Ang-(1-7) promoted nonphlogistic mononuclear cell influx alongside increased levels of CCL2, IL-10, and macrophage polarization toward a regulatory phenotype. Ang-(1-7) induction of CCL2 and mononuclear cell migration was also dependent on MasR and MEK/ERK. Of note, MasR was upregulated during the resolution phase of inflammation, and its pharmacological inhibition or genetic deficiency impaired mononuclear cell recruitment during self-resolving models of LPS pleurisy and E. coli peritonitis. Inhibition/absence of MasR was associated with reduced CCL2 levels, impaired phagocytosis of bacteria, efferocytosis, and delayed resolution of inflammation. In summary, we have uncovered a potentially novel proresolving feature of Ang-(1-7), namely the recruitment of mononuclear cells favoring efferocytosis, phagocytosis, and resolution of inflammation. Mechanistically, cell migration was dependent on MasR, CCR2, and the MEK/ERK pathway. | |
dc.format | Electronic | |
dc.language | eng | |
dc.publisher | AMER SOC CLINICAL INVESTIGATION INC | |
dc.relation.ispartof | JCI Insight | |
dc.relation.isbasedon | 10.1172/jci.insight.147819 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject.mesh | Angiotensin I | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Cells, Cultured | |
dc.subject.mesh | Disease Models, Animal | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Inflammation | |
dc.subject.mesh | MAP Kinase Signaling System | |
dc.subject.mesh | Macrophages | |
dc.subject.mesh | Male | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Mice, Inbred BALB C | |
dc.subject.mesh | Monocytes | |
dc.subject.mesh | Peptide Fragments | |
dc.subject.mesh | Peritonitis | |
dc.subject.mesh | Phagocytosis | |
dc.subject.mesh | Phenotype | |
dc.subject.mesh | Proto-Oncogene Mas | |
dc.subject.mesh | Receptors, CCR2 | |
dc.subject.mesh | Monocytes | |
dc.subject.mesh | Cells, Cultured | |
dc.subject.mesh | Macrophages | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Mice, Inbred BALB C | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Peritonitis | |
dc.subject.mesh | Disease Models, Animal | |
dc.subject.mesh | Inflammation | |
dc.subject.mesh | Angiotensin I | |
dc.subject.mesh | Peptide Fragments | |
dc.subject.mesh | Phagocytosis | |
dc.subject.mesh | MAP Kinase Signaling System | |
dc.subject.mesh | Phenotype | |
dc.subject.mesh | Male | |
dc.subject.mesh | Receptors, CCR2 | |
dc.subject.mesh | Proto-Oncogene Mas | |
dc.title | Angiotensin-(1-7)/MasR axis promotes migration of monocytes/macrophages with a regulatory phenotype to perform phagocytosis and efferocytosis. | |
dc.type | Journal Article | |
utslib.citation.volume | 7 | |
utslib.location.activity | United States | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
utslib.copyright.status | open_access | * |
dc.date.updated | 2023-02-06T03:24:22Z | |
pubs.issue | 1 | |
pubs.publication-status | Published online | |
pubs.volume | 7 | |
utslib.citation.issue | 1 |
Abstract:
Nonphlogistic migration of macrophages contributes to the clearance of pathogens and apoptotic cells, a critical step for the resolution of inflammation and return to homeostasis. Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system that acts through Mas receptor (MasR). Ang-(1-7) has recently emerged as a novel proresolving mediator, yet Ang-(1-7) resolution mechanisms are not fully determined. Herein, Ang-(1-7) stimulated migration of human and murine monocytes/macrophages in a MasR-, CCR2-, and MEK/ERK1/2-dependent manner. Pleural injection of Ang-(1-7) promoted nonphlogistic mononuclear cell influx alongside increased levels of CCL2, IL-10, and macrophage polarization toward a regulatory phenotype. Ang-(1-7) induction of CCL2 and mononuclear cell migration was also dependent on MasR and MEK/ERK. Of note, MasR was upregulated during the resolution phase of inflammation, and its pharmacological inhibition or genetic deficiency impaired mononuclear cell recruitment during self-resolving models of LPS pleurisy and E. coli peritonitis. Inhibition/absence of MasR was associated with reduced CCL2 levels, impaired phagocytosis of bacteria, efferocytosis, and delayed resolution of inflammation. In summary, we have uncovered a potentially novel proresolving feature of Ang-(1-7), namely the recruitment of mononuclear cells favoring efferocytosis, phagocytosis, and resolution of inflammation. Mechanistically, cell migration was dependent on MasR, CCR2, and the MEK/ERK pathway.
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