Degranulating Neutrophils Promote Leukotriene B4 Production by Infected Macrophages To Kill Leishmania amazonensis Parasites

The Journal of Immunology : Official Journal of the American Association of Immunologists
Natália TavaresCláudia Brodskyn

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 L...Continue Reading

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Citations

Dec 9, 2017·Frontiers in Immunology·Graziele Quintela-CarvalhoValeria M Borges
May 24, 2019·Journal of Leukocyte Biology·Filipe S Pereira-DutraPatrícia T Bozza
Jun 12, 2020·Emerging Microbes & Infections·Icaro Bonyek-SilvaNatalia M Tavares
Sep 7, 2016·Parasites & Vectors·Mariana M ChavesRobson Coutinho-Silva
Mar 19, 2021·Frontiers in Immunology·Katiuska PasselliFabienne Tacchini-Cottier

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