Clearance of apoptotic cells by macrophages induces regulatory phenotype and involves stimulation of cd36 and platelet-activating factor receptor

Ferracini, M., Rios, F.J.O. , Pecenin, M. and Jancar, S. (2013) Clearance of apoptotic cells by macrophages induces regulatory phenotype and involves stimulation of cd36 and platelet-activating factor receptor. Mediators of Inflammation, 2013, p. 950273. (doi: 10.1155/2013/950273)

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Abstract

Phagocytosis of apoptotic cells (efferocytosis) induces macrophage differentiation towards a regulatory phenotype (IL-10high/IL-12p40low). 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-10high/IL-12p40low, 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rios, Dr Francisco
Authors: Ferracini, M., Rios, F.J.O., Pecenin, M., and Jancar, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Mediators of Inflammation
Publisher:Hindawi Publishing Corporation
ISSN:0962-9351
ISSN (Online):1466-1861
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Mediators of Inflammation 2013:950273
Publisher Policy:Reproduced under a Creative Commons License

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