Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/15185
Title: Degranulating Neutrophils Promote Leukotriene B4 Production by Infected Macrophages To Kill Leishmania amazonensis Parasites
Authors: Tavares, Natália
Afonso, Lilian Maria
Suarez, Martha
Ampuero, Mariana
Prates, Deboraci Brito
Santos, Théo Araújo
Barral Netto, Manoel
DosReis, George Alexandre
Borges, Valéria de Matos
Brodskyn, Claudia Ida
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, Brasil
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, Brasil
Abstract: Neutrophils mediate early responses against pathogens, and they become activated during endothelial transmigration toward the inflammatory site. In the current study, human neutrophils were activated in vitro with immobilized extracellular matrix proteins, such as fibronectin (FN), collagen, and laminin. Neutrophil activation by FN, but not other extracellular matrix proteins, induces the release of the granules' contents, measured as matrix metalloproteinase 9 and neutrophil elastase activity in culture supernatant, as well as reactive oxygen species production. Upon contact with Leishmania amazonensis-infected macrophages, these FN-activated neutrophils reduce the parasite burden through a mechanism independent of cell contact. The release of granule proteases, such as myeloperoxidase, neutrophil elastase, and matrix metalloproteinase 9, activates macrophages through TLRs, leading to the production of inflammatory mediators, TNF-α and leukotriene B4 (LTB4), which are involved in parasite killing by infected macrophages. The pharmacological inhibition of degranulation reverted this effect, abolishing LTB4 and TNF production. Together, these results suggest that FN-driven degranulation of neutrophils induces the production of LTB4 and TNF by infected macrophages, leading to the control of Leishmania infection.
Keywords: Leishmania
Leishmania mexicana
Leishmaniasis cutaneous
Cell degranulation
Fibronectins
Humans
Macrophages
Microscopy electron
Neutrophils
Issue Date: 2016
Publisher: American Association of Immunologists, Inc.
Citation: TAVARES, N. et al. Degranulating Neutrophils Promote Leukotriene B4 Production by Infected Macrophages To Kill Leishmania amazonensis Parasites. The Journal of Immunology, v. 196, p. 1865-1873, 2016.
DOI: 10.4049/jimmunol.1502224
ISSN: 0022-1767
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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