Participação do PAF-R na fagocitose de células apoptóticas, no fenótipo de macrófagos e na imunossupressão causada por terapia fotodinâmica.

Ferracini, Matheus

doi:10.11606/T.42.2014.tde-15122014-090538

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Doctoral Thesis

DOI

https://doi.org/10.11606/T.42.2014.tde-15122014-090538

Document

Doctoral Thesis

Author

Ferracini, Matheus (Catálogo USP)

Full name

Matheus Ferracini

Institute/School/College

Instituto de Ciências Biomédicas

Knowledge Area

Immunology

Date of Defense

2014-09-18

Published

São Paulo, 2014

Supervisor

Negro, Sonia Jancar (Catálogo USP)

Committee

Negro, Sonia Jancar (President)
Chammas, Roger
Faccioli, Lucia Helena
Lepique, Ana Paula
Starobinas, Nancy

Title in Portuguese

Participação do PAF-R na fagocitose de células apoptóticas, no fenótipo de macrófagos e na imunossupressão causada por terapia fotodinâmica.

Keywords in Portuguese

Fagocitose de células apoptóticas
Fenótipo de macrófagos
Macrófago
Receptor do PAF
Receptor scavenger CD36
Terapia fotodinâmica

Abstract in Portuguese

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.

Title in English

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

Keywords in English

Macrophage
Macrophage phenotypes
PAF receptor
Phagocytosis of apoptotic cells
Photodynamic therapy
Scavenger receptor CD36

Abstract in English

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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Publishing Date

2014-12-16

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