Participation of PAF-R in the phagocytosis of apoptotic cells, in macrophage phenotype and in the immunosuppression caused by photodynamic therapy.

Author(s)

Matheus Ferracini

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2014-09-18

Examining board members

Sonia Jancar Negro; Roger Chammas; Lucia Helena Faccioli; Ana Paula Lepique; Nancy Starobinas

• Advisor: Sonia Jancar Negro

Abstract

Macrophages (Mp) produce PAF and PAF-R and scavenge altered particles via CD36. oxLDL uptake requires association CD36/PAF-R. We analyzed that on efferocytosis. PAF-R and lipid rafts (LR) blockage inhibited efferocytosis. Efferocytosis induced association CD36/PAF-R and both with LR marker protein, and induced IL-10 and IL-12p40. PAF-R and COX-2 blockage inhibited more IL-10, suggesting that efferocytosis depends on PAF-R/CD36 interaction in LR and that this induces prostanoids and regulatory profile. Mp acquire different phenotypes. PAF-R participation in that was analyzed. PAF-R blockage before stimuli (IFN-g/LPS, IL-4 or IgG-SRBC/LPS) inhibited markers MCP-1, TNF-a, iNOS, mannose receptor, arginase-1 and IL-10, but not IL-12p40, suggesting that PAF-R modulates Mp phenotype. PAF and PAF-like are generated by oxidative stressors. PAF-R activation induces systemic immunosuppression (SI). We showed that photodynamic therapy (PDT) in vitro generated PAF-R ligands and in vivo inhibited CHS reaction in WT, but not PAF-R KO, suggesting that PDT induces SI via PAF-R. (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 Opportunities: Scholarships in Brazil - Doctorate