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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Ferracini, Matheus [1] ; Rios, Francisco J. O. [1, 2] ; Pecenin, Mateus [1] ; Jancar, Sonia [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, BR-05508000 Sao Paulo - Brazil
[2] Univ Glasgow, Inst Cardiovasc & Med Sci, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark - Scotland
Total Affiliations: 2
Document type: Journal article
Source: Mediators of Inflammation; 2013.
Web of Science Citations: 25
Abstract

Phagocytosis of apoptotic cells (efferocytosis) induces macrophage differentiation towards a regulatory phenotype (IL-10(high)/IL12p40(low)). 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 indexwas determined. Blockage of PAFRwith antagonists orCD36 with specific antibodies inhibited the phagocytosis of AC (similar to 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-beta-cyclodextrin reduced AC phagocytosis. Efferocytosis induced a pattern of cytokine production, IL-10(high)/IL-12p40(low), that is, characteristic of a regulatory phenotype. LPS potentiated the efferocytosis-induced production of IL-10, and thiswas 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. (AU)

FAPESP's process: 09/03368-3 - The PAF receptor on macrophage polarization to M1 and M2 phenotype: localization, interactions and signaling pathways
Grantee:Matheus Ferracini
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 06/03982-5 - Molecular aspects involved in leukocytes microbicidal and inflammatory activities in the lung
Grantee:Sônia Jancar
Support type: Research Projects - Thematic Grants