The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype.

Autor:	Ortiz Wilczyñski JM; Institute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, Argentina., Mena HA; Institute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, Argentina., Ledesma MM; Institute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, Argentina., Olexen CM; Institute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, Argentina.; Institute of Pharmacology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina., Podaza E; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, United States., Schattner M; Institute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, Argentina., Negrotto S; Institute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, Argentina., Errasti AE; Institute of Pharmacology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina., Carrera Silva EA; Institute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, Argentina.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jun 16; Vol. 14, pp. 1162671. Date of Electronic Publication: 2023 Jun 16 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1162671
Abstrakt:	Monocytes (Mo) are highly plastic myeloid cells that differentiate into macrophages after extravasation, playing a pivotal role in the resolution of inflammation and regeneration of injured tissues. Wound-infiltrated monocytes/macrophages are more pro-inflammatory at early time points, while showing anti-inflammatory/pro-reparative phenotypes at later phases, with highly dynamic switching depending on the wound environment. Chronic wounds are often arrested in the inflammatory phase with hampered inflammatory/repair phenotype transition. Promoting the tissue repair program switching represents a promising strategy to revert chronic inflammatory wounds, one of the major public health loads. We found that the synthetic lipid C8-C1P primes human CD14 + monocytes, restraining the inflammatory activation markers (HLA-DR, CD44, and CD80) and IL-6 when challenged with LPS, and preventing apoptosis by inducing BCL-2. We also observed increased pseudo-tubule formation of human endothelial-colony-forming cells (ECFCs) when stimulated with the C1P-macrophages secretome. Moreover, C8-C1P-primed monocytes skew differentiation toward pro-resolutive-like macrophages, even in the presence of inflammatory PAMPs and DAMPs by increasing anti-inflammatory and pro-angiogenic gene expression patterns. All these results indicate that C8-C1P could restrain M1 skewing and promote the program of tissue repair and pro-angiogenic macrophage. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Ortiz Wilczyñski, Mena, Ledesma, Olexen, Podaza, Schattner, Negrotto, Errasti and Carrera Silva.)
Databáze:	MEDLINE
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