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Thèse de Doctorat
DOI
https://doi.org/10.11606/T.42.2014.tde-15122014-090538
Document
Auteur
Nom complet
Matheus Ferracini
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2014
Directeur
Jury
Negro, Sonia Jancar (Président)
Chammas, Roger
Faccioli, Lucia Helena
Lepique, Ana Paula
Starobinas, Nancy
Titre en portugais
Participação do PAF-R na fagocitose de células apoptóticas, no fenótipo de macrófagos e na imunossupressão causada por terapia fotodinâmica.
Mots-clés en portugais
Fagocitose de células apoptóticas
Fenótipo de macrófagos
Macrófago
Receptor do PAF
Receptor scavenger CD36
Terapia fotodinâmica
Resumé en portugais
Macrófagos (Mf) produzem PAF e PAF-R e eliminam partículas alteradas via CD36. Uptake de oxLDL requer associação CD36/PAF-R. Avaliamos isto na eferocitose. Bloqueio do PAF-R e de lipid rafts (LR) inibiu eferocitose. Esta induziu associação PAF-R/CD36 e destes com flotilina-1 (marca LR). Eferocitose induziu IL-10 e IL-12p40. Bloqueio do PAF-R inibiu mais IL-10 e inibição da COX-2 teve efeito similar, sugerindo que eferocitose depende da interação PAF-R/CD36 em LR e que isto induz prostanoides e perfil regulador. Mf adquirirem diferentes fenótipos. Estudamos a participação do PAF-R. Bloqueio do PAF-R antes dos estímulos (IFN-g/LPS, IL-4 ou IgG-SRBC/LPS) inibiu marcadores MCP-1, TNF-a, iNOS, receptor manose, arginase-1 e IL-10, mas não IL-12p40, sugerindo que PAF-R modula fenótipo de Mf. PAF e PAF-like são gerados por estressores oxidativos. Ativação do PAF-R induz imunossupressão sistêmica (IS). Mostramos que terapia fotodinâmica (PDT) in vitro gerou ligantes do PAF-R e in vivo inibiu reação de CHS em WT, mas não em PAF-R KO, sugerindo que PDT induz IS via PAF-R.
Titre en anglais
Participation of PAF-R in the phagocytosis of apoptotic cells, in macrophage phenotype and in the immunosuppression caused by photodynamic therapy.
Mots-clés en anglais
Macrophage
Macrophage phenotypes
PAF receptor
Phagocytosis of apoptotic cells
Photodynamic therapy
Scavenger receptor CD36
Resumé en anglais
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.
 
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Date de Publication
2014-12-16
 
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