Neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages.

Neutrophil extracellular traps (NETs) are web-like structures, which are released upon neutrophil activation. It has previously been demonstrated that NETs are present in atherosclerotic lesions of both humans and animal models thus playing a decisive role in atherosclerosis. Besides, macrophages ha...

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Autores principales:	Andreas Conforti, Thorsten Wahlers, Adnana Paunel-Görgülü
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c91cf749412477c8ff078c206dfd24a
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spelling	oai:doaj.org-article:6c91cf749412477c8ff078c206dfd24a2021-12-02T20:12:39ZNeutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages.1932-620310.1371/journal.pone.0259894https://doaj.org/article/6c91cf749412477c8ff078c206dfd24a2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0259894https://doaj.org/toc/1932-6203Neutrophil extracellular traps (NETs) are web-like structures, which are released upon neutrophil activation. It has previously been demonstrated that NETs are present in atherosclerotic lesions of both humans and animal models thus playing a decisive role in atherosclerosis. Besides, macrophages have a crucial role in disease progression, whereby classically activated M1 macrophages sustain inflammation and alternatively activated M2 macrophages display anti-inflammatory effects. Although NETs and macrophages were found to colocalize in atherosclerotic lesions, the impact of NETs on macrophage function is not fully understood. In the present study, we aimed to investigate the effect of NETs on human and murine macrophages in respect to the expression of pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and uptake of oxidized LDL (oxLDL) in vitro. Human THP-1 and murine bone marrow-derived macrophages were cultured under M1 (LPS + IFN-γ)- and M2a (IL-4)-polarizing culture conditions and treated with NETs. To mimic intraplaque regions, cells were additionally cultured under hypoxic conditions. NETs significantly increased the expression of IL-1β, TNF-α and IL-6 in THP-M1 macrophages under normoxia but suppressed their expression in murine M1 macrophages under hypoxic conditions. Notably, NETs increased the number of oxLDL-positive M1 and M2 human and murine macrophages under normoxia, but did not influence formation of murine foam cells under hypoxia. However, oxLDL uptake did not strongly correlate with the expression of the LDL receptor CD36. Besides, upregulated MMP-9 expression and secretion by macrophages was detected in the presence of NETs. Again, hypoxic culture conditions dampened NETs effects. These results suggest that NETs may favor foam cell formation and plaque vulnerability, but exert opposite effects in respect to the inflammatory response of human and murine M1 macrophages. Moreover, effects of NETs on macrophages' phenotype are altered under hypoxia.Andreas ConfortiThorsten WahlersAdnana Paunel-GörgülüPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0259894 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andreas Conforti Thorsten Wahlers Adnana Paunel-Görgülü Neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages.
description	Neutrophil extracellular traps (NETs) are web-like structures, which are released upon neutrophil activation. It has previously been demonstrated that NETs are present in atherosclerotic lesions of both humans and animal models thus playing a decisive role in atherosclerosis. Besides, macrophages have a crucial role in disease progression, whereby classically activated M1 macrophages sustain inflammation and alternatively activated M2 macrophages display anti-inflammatory effects. Although NETs and macrophages were found to colocalize in atherosclerotic lesions, the impact of NETs on macrophage function is not fully understood. In the present study, we aimed to investigate the effect of NETs on human and murine macrophages in respect to the expression of pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and uptake of oxidized LDL (oxLDL) in vitro. Human THP-1 and murine bone marrow-derived macrophages were cultured under M1 (LPS + IFN-γ)- and M2a (IL-4)-polarizing culture conditions and treated with NETs. To mimic intraplaque regions, cells were additionally cultured under hypoxic conditions. NETs significantly increased the expression of IL-1β, TNF-α and IL-6 in THP-M1 macrophages under normoxia but suppressed their expression in murine M1 macrophages under hypoxic conditions. Notably, NETs increased the number of oxLDL-positive M1 and M2 human and murine macrophages under normoxia, but did not influence formation of murine foam cells under hypoxia. However, oxLDL uptake did not strongly correlate with the expression of the LDL receptor CD36. Besides, upregulated MMP-9 expression and secretion by macrophages was detected in the presence of NETs. Again, hypoxic culture conditions dampened NETs effects. These results suggest that NETs may favor foam cell formation and plaque vulnerability, but exert opposite effects in respect to the inflammatory response of human and murine M1 macrophages. Moreover, effects of NETs on macrophages' phenotype are altered under hypoxia.
format	article
author	Andreas Conforti Thorsten Wahlers Adnana Paunel-Görgülü
author_facet	Andreas Conforti Thorsten Wahlers Adnana Paunel-Görgülü
author_sort	Andreas Conforti
title	Neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages.
title_short	Neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages.
title_full	Neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages.
title_fullStr	Neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages.
title_full_unstemmed	Neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages.
title_sort	neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized ldl by human and murine macrophages.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/6c91cf749412477c8ff078c206dfd24a
work_keys_str_mv	AT andreasconforti neutrophilextracellulartrapsmodulateinflammatorymarkersanduptakeofoxidizedldlbyhumanandmurinemacrophages AT thorstenwahlers neutrophilextracellulartrapsmodulateinflammatorymarkersanduptakeofoxidizedldlbyhumanandmurinemacrophages AT adnanapaunelgorgulu neutrophilextracellulartrapsmodulateinflammatorymarkersanduptakeofoxidizedldlbyhumanandmurinemacrophages
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Neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages.

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