| Texto completo | |
| Autor(es): |
Goncalves, Mariana Torrente
[1]
;
Squaiella-Baptistao, Carla Cristina
[1]
;
Pidde, Giselle
[1]
;
Lopes, Priscila Hess
[1]
;
da Silva Nunes, Iseu
[2]
;
Tambourgi, Denise V.
[1]
Número total de Autores: 6
|
| Afiliação do(s) autor(es): | [1] Inst Butantan, Immunochem Lab, Sao Paulo - Brazil
[2] Farmabrasilis, Campinas - Brazil
Número total de Afiliações: 2
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Mediators of Inflammation; v. 2020, NOV 24 2020. |
| Citações Web of Science: | 0 |
| Resumo | |
P-MAPA is a complex compound, derived from Aspergillus oryzae cultures, that has shown immunomodulatory properties in infection and cancer animal models. Despite promising results in these models, the mechanisms of cellular activation by P-MAPA, suggested to be Toll-like receptor- (TLR-) dependent, and its effect on human immune cells, remain unclear. Using an ex vivo model of human whole blood, the effects of P-MAPA on complement system activation, production of cytokines, and the expression of complement receptors (CD11b, C5aR, and C3aR), TLR2, TLR4, and the coreceptor CD14 were analyzed in neutrophils and monocytes. P-MAPA induced complement activation in human blood, detected by increased levels of C3a, C5a, and SC5b-9 in plasma. As a consequence, CD11b expression increased and C5aR decreased upon activation, while C3aR expression remained unchanged in leukocytes. TLR2 and TLR4 expressions were not modulated by P-MAPA treatment on neutrophils, but TLR4 expression was reduced in monocytes, while CD14 expression increased in both cell types. P-MAPA also induced the production of TNF-alpha, IL-8, and IL-12 and oxidative burst, measured by peroxynitrite levels, in human leukocytes. Complement inhibition with compstatin showed that P-MAPA-induced complement activation drives modulation of C5aR, but not of CD11b, suggesting that P-MAPA acts through both complement-dependent and complement-independent mechanisms. Compstatin also significantly reduced the peroxynitrite generation. Altogether, our results show that P-MAPA induced proinflammatory response in human leukocytes, which is partially mediated by complement activation. Our data contribute to elucidate the complement-dependent and complement-independent mechanisms of P-MAPA, which ultimately result in immune cell activation and in its immunomodulatory properties in infection and cancer animal models. (AU) | |
| Processo FAPESP: | 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular |
| Beneficiário: | Hugo Aguirre Armelin |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |
| Processo FAPESP: | 12/05306-8 - Ação do imunomodulador P-MAPA sobre o Sistema Complemento e Receptores do tipo Toll em modelo de inflamação induzida por LPS |
| Beneficiário: | Mariana Torrente Gonçalves |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |