Clearance of Apoptotic Cells by Macrophages Induces Regulatory Phenotype and Involves Stimulation of CD36 and Platelet-Activating Factor ReceptorReport as inadecuate




Clearance of Apoptotic Cells by Macrophages Induces Regulatory Phenotype and Involves Stimulation of CD36 and Platelet-Activating Factor Receptor - Download this document for free, or read online. Document in PDF available to download.

Mediators of InflammationVolume 2013 2013, Article ID 950273, 8 pages

Research Article

Department of Immunology, Biomedical Sciences Institute, University of São Paulo, Avenue Professor Lineu Prestes 1730, ICB IV, Sala 140-146, 05508-000 São Paulo, SP, Brazil

Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK

Received 10 July 2013; Revised 14 September 2013; Accepted 8 October 2013

Academic Editor: Hidde Bult

Copyright © 2013 Matheus Ferracini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Phagocytosis of apoptotic cells efferocytosis induces macrophage differentiation towards a regulatory phenotype IL-10

-IL-12p40

. CD36 is involved in the recognition of apoptotic cells AC, and we have shown that the platelet-activating factor receptor PAFR is also involved. Here, we investigated the contribution of PAFR and CD36 to efferocytosis and to the establishment of a regulatory macrophage phenotype. Mice bone marrow-derived macrophages were cocultured with apoptotic thymocytes, and the phagocytic index was determined. Blockage of PAFR with antagonists or CD36 with specific antibodies inhibited the phagocytosis of AC ~70–80%. Using immunoprecipitation and confocal microscopy, we showed that efferocytosis increased the CD36 and PAFR colocalisation in the macrophage plasma membrane; PAFR and CD36 coimmunoprecipitated with flotillin-1, a constitutive lipid raft protein, and disruption of these membrane microdomains by methyl-β-cyclodextrin reduced AC phagocytosis. Efferocytosis induced a pattern of cytokine production, IL-10

-IL-12p40

, that is, characteristic of a regulatory phenotype. LPS potentiated the efferocytosis-induced production of IL-10, and this was prevented by blocking PAFR or CD36. It can be concluded that phagocytosis of apoptotic cells engages CD36 and PAFR, possibly in lipid rafts, and this is required for optimal efferocytosis and the establishment of the macrophage regulatory phenotype.





Author: Matheus Ferracini, Francisco J. O. Rios, Mateus Pecenin, and Sonia Jancar

Source: https://www.hindawi.com/



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