P-MAPA, a Fungi-Derived Immunomodulatory Compound, Induces a Proinflammatory Response in a Human Whole Blood Model
Joint Authors
Squaiella-Baptistão, Carla Cristina
Pidde, Giselle
Gonçalves, Mariana Torrente
Lopes, Priscila Hess
da Silva Nunes, Iseu
Tambourgi, Denise V.
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-11-24
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
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-α, 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.
American Psychological Association (APA)
Gonçalves, Mariana Torrente& Squaiella-Baptistão, Carla Cristina& Pidde, Giselle& Lopes, Priscila Hess& da Silva Nunes, Iseu& Tambourgi, Denise V.. 2020. P-MAPA, a Fungi-Derived Immunomodulatory Compound, Induces a Proinflammatory Response in a Human Whole Blood Model. Mediators of Inflammation،Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1192151
Modern Language Association (MLA)
Gonçalves, Mariana Torrente…[et al.]. P-MAPA, a Fungi-Derived Immunomodulatory Compound, Induces a Proinflammatory Response in a Human Whole Blood Model. Mediators of Inflammation No. 2020 (2020), pp.1-13.
https://search.emarefa.net/detail/BIM-1192151
American Medical Association (AMA)
Gonçalves, Mariana Torrente& Squaiella-Baptistão, Carla Cristina& Pidde, Giselle& Lopes, Priscila Hess& da Silva Nunes, Iseu& Tambourgi, Denise V.. P-MAPA, a Fungi-Derived Immunomodulatory Compound, Induces a Proinflammatory Response in a Human Whole Blood Model. Mediators of Inflammation. 2020. Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1192151
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192151