Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices

Complement activation is key to anti-microbial defenses by directly acting on microbes and indirectly by triggering cellular immune responses. Complement activation may also contribute to the pathogenesis of numerous inflammatory and immunological diseases. Consequently, intense research focuses on...

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Autores principales:	Sinan Muldur, Douangsone D. Vadysirisack, Sharan Ragunathan, Yalan Tang, Alonso Ricardo, Camil Elie Sayegh, Daniel Irimia
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	complement neutrophil microfluidic “lab-on-a-chip phagocytosis infection eculizumab Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/c7e1234c80aa497e8dd7643e9305cd27
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spelling	oai:doaj.org-article:c7e1234c80aa497e8dd7643e9305cd272021-11-30T19:45:08ZHuman Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices1664-322410.3389/fimmu.2021.777932https://doaj.org/article/c7e1234c80aa497e8dd7643e9305cd272021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.777932/fullhttps://doaj.org/toc/1664-3224Complement activation is key to anti-microbial defenses by directly acting on microbes and indirectly by triggering cellular immune responses. Complement activation may also contribute to the pathogenesis of numerous inflammatory and immunological diseases. Consequently, intense research focuses on developing therapeutics that block pathology-causing complement activation while preserving anti-microbial complement activities. However, the pace of research is slowed down significantly by the limitations of current tools for evaluating complement-targeting therapeutics. Moreover, the effects of potential therapeutic agents on innate immune cells, like neutrophils, are not fully understood. Here, we employ microfluidic assays and measure chemotaxis, phagocytosis, and swarming changes in human neutrophils ex vivo in response to various complement-targeting agents. We show that whereas complement factor 5 (C5) cleavage inhibitor eculizumab blocks all neutrophil anti-microbial functions, newer compounds like the C5 cleavage inhibitor RA101295 and C5a receptor antagonist avacopan inhibit chemotaxis and swarming while preserving neutrophil phagocytosis. These results highlight the utility of microfluidic neutrophil assays in evaluating potential complement-targeting therapeutics.Sinan MuldurSinan MuldurDouangsone D. VadysirisackSharan RagunathanYalan TangAlonso RicardoCamil Elie SayeghDaniel IrimiaDaniel IrimiaFrontiers Media S.A.articlecomplementneutrophilmicrofluidic “lab-on-a-chipphagocytosisinfectioneculizumabImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	complement neutrophil microfluidic “lab-on-a-chip phagocytosis infection eculizumab Immunologic diseases. Allergy RC581-607
spellingShingle	complement neutrophil microfluidic “lab-on-a-chip phagocytosis infection eculizumab Immunologic diseases. Allergy RC581-607 Sinan Muldur Sinan Muldur Douangsone D. Vadysirisack Sharan Ragunathan Yalan Tang Alonso Ricardo Camil Elie Sayegh Daniel Irimia Daniel Irimia Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices
description	Complement activation is key to anti-microbial defenses by directly acting on microbes and indirectly by triggering cellular immune responses. Complement activation may also contribute to the pathogenesis of numerous inflammatory and immunological diseases. Consequently, intense research focuses on developing therapeutics that block pathology-causing complement activation while preserving anti-microbial complement activities. However, the pace of research is slowed down significantly by the limitations of current tools for evaluating complement-targeting therapeutics. Moreover, the effects of potential therapeutic agents on innate immune cells, like neutrophils, are not fully understood. Here, we employ microfluidic assays and measure chemotaxis, phagocytosis, and swarming changes in human neutrophils ex vivo in response to various complement-targeting agents. We show that whereas complement factor 5 (C5) cleavage inhibitor eculizumab blocks all neutrophil anti-microbial functions, newer compounds like the C5 cleavage inhibitor RA101295 and C5a receptor antagonist avacopan inhibit chemotaxis and swarming while preserving neutrophil phagocytosis. These results highlight the utility of microfluidic neutrophil assays in evaluating potential complement-targeting therapeutics.
format	article
author	Sinan Muldur Sinan Muldur Douangsone D. Vadysirisack Sharan Ragunathan Yalan Tang Alonso Ricardo Camil Elie Sayegh Daniel Irimia Daniel Irimia
author_facet	Sinan Muldur Sinan Muldur Douangsone D. Vadysirisack Sharan Ragunathan Yalan Tang Alonso Ricardo Camil Elie Sayegh Daniel Irimia Daniel Irimia
author_sort	Sinan Muldur
title	Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices
title_short	Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices
title_full	Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices
title_fullStr	Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices
title_full_unstemmed	Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices
title_sort	human neutrophils respond to complement activation and inhibition in microfluidic devices
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c7e1234c80aa497e8dd7643e9305cd27
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Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices

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