Angiotensin-(1-7)/MasR axis promotes migration of monocytes/macrophages with a regulatory phenotype to perform phagocytosis and efferocytosis

• DOI: 10.1172/jci.insight.147819
• Publication Date: 2021-12-07T17:01:04Z
• Authors: Isabella Zaidan; Luciana P. Tavares; Michelle A. Sugimoto; Kátia M. Lima; Graziele L. Negre...; Lívia C.R. Teixeira; Thais C. Miranda; Bruno V.S. Valiate; Allysson Cramer; Juliana Priscila ...; Gabriel H. Campol...; Jéssica A.M. Souza; Laís C. Grossi; Vanessa Pinho; Maria Jose Campag...; Robson A.S. Santos; Mauro M. Teixeira; Izabela Galvão; Lirlândia P. Sousa
• Keywords: efferocytosis; CCR2

Nonphlogistic migration of macrophages contributes to the clearance pathogens and apoptotic cells, a critical step for resolution inflammation return homeostasis. Angiotensin-(1-7) [Ang-(1-7)] is heptapeptide renin-angiotensin system that acts through Mas receptor (MasR). Ang-(1-7) has recently emerged as novel proresolving mediator, yet mechanisms are not fully determined. Herein, stimulated human murine monocytes/macrophages in MasR-, CCR2-, MEK/ERK1/2-dependent manner. Pleural injection promoted nonphlogistic mononuclear cell influx alongside increased levels CCL2, IL-10, macrophage polarization toward regulatory phenotype. induction CCL2 was also dependent on MasR MEK/ERK. Of note, upregulated during phase inflammation, its pharmacological inhibition or genetic deficiency impaired recruitment self-resolving models LPS pleurisy E. coli peritonitis. Inhibition/absence associated with reduced levels, phagocytosis bacteria, efferocytosis, delayed inflammation. In summary, we have uncovered potentially feature Ang-(1-7), namely cells favoring phagocytosis, Mechanistically, MasR, CCR2, MEK/ERK pathway.