Silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in RAW 264.7 macrophages and MPRO 2.1 neutrophils

Engineered nanomaterials (ENM) are being used in a wide range of consumer products and pharmaceuticals; hence, there is an increasing risk for human exposure and potential adverse outcomes. The immune system, vital in host defense and protection against environmental agents, is typically initiated a...

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Main Authors: Nasser B. Alsaleh, Valerie C. Minarchick, Ryan P. Mendoza, Bipin Sharma, Ramakrishna Podila, Jared M. Brown
Format: Article
Language:English
Published: Taylor & Francis Group 2019-01-01
Series:Journal of Immunotoxicology
Subjects:
Online Access:http://dx.doi.org/10.1080/1547691X.2019.1588928
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author Nasser B. Alsaleh
Valerie C. Minarchick
Ryan P. Mendoza
Bipin Sharma
Ramakrishna Podila
Jared M. Brown
author_facet Nasser B. Alsaleh
Valerie C. Minarchick
Ryan P. Mendoza
Bipin Sharma
Ramakrishna Podila
Jared M. Brown
author_sort Nasser B. Alsaleh
collection DOAJ
description Engineered nanomaterials (ENM) are being used in a wide range of consumer products and pharmaceuticals; hence, there is an increasing risk for human exposure and potential adverse outcomes. The immune system, vital in host defense and protection against environmental agents, is typically initiated and executed by innate effector immune cells including macrophages and neutrophils. Previous literature has reported the immune system as a major target of ENM toxicity; however, there is inconsistency regarding the immunotoxicity of ENM. This could be attributed to differences in ENM physicochemical properties, cellular models examined, biocorona formation, etc. Thus, the current study examined the toxicity and immunomodulatory effects of silver nanoparticles (AgNP), one of the most utilized ENM in consumer and medical products, in two key innate immune cell models, e.g. RAW 264.7 cells (macrophages) and differentiated MPRO 2.1 cells (promyelocytes/neutrophils). The results showed that despite a generation of reactive oxygen species, exposure to 20 nm citrate-coated AgNP was not associated with major oxidative damage, inflammatory responses, nor cytotoxicity. Nevertheless, and most importantly, pre-exposure to the AgNP for 24 h enhanced RAW 264.7 cell phagocytic ability as well as the release of inflammatory cytokine interleukin-6 in response to lipopolysaccharide (LPS). In MPRO 2.1 cells, AgNP pre-exposure also resulted in enhanced phagocytic ability; however, these cells manifest reduced cell degranulation (elastase release) and oxidative burst in response to phorbol myristate acetate (PMA). Taken together, these findings indicated to us that exposure to AgNP, despite not being directly (cyto)toxic to these cells, had the potential to alter immune cell responses. The findings underscore the import of assessing immune cell function post-exposure to ENM beyond the standard endpoints such as oxidative stress and cytotoxicity. In addition, these findings further illustrate the importance of understanding the underlying molecular mechanisms of ENM-cellular interactions, particularly in the immune system.
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spelling doaj.art-209685282b284f4988def548c9a0e2ed2022-12-21T18:32:27ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012019-01-01161637310.1080/1547691X.2019.15889281588928Silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in RAW 264.7 macrophages and MPRO 2.1 neutrophilsNasser B. Alsaleh0Valerie C. Minarchick1Ryan P. Mendoza2Bipin Sharma3Ramakrishna Podila4Jared M. Brown5University of Colorado Anschutz Medical CampusUniversity of Colorado Anschutz Medical CampusUniversity of Colorado Anschutz Medical CampusClemson UniversityClemson UniversityUniversity of Colorado Anschutz Medical CampusEngineered nanomaterials (ENM) are being used in a wide range of consumer products and pharmaceuticals; hence, there is an increasing risk for human exposure and potential adverse outcomes. The immune system, vital in host defense and protection against environmental agents, is typically initiated and executed by innate effector immune cells including macrophages and neutrophils. Previous literature has reported the immune system as a major target of ENM toxicity; however, there is inconsistency regarding the immunotoxicity of ENM. This could be attributed to differences in ENM physicochemical properties, cellular models examined, biocorona formation, etc. Thus, the current study examined the toxicity and immunomodulatory effects of silver nanoparticles (AgNP), one of the most utilized ENM in consumer and medical products, in two key innate immune cell models, e.g. RAW 264.7 cells (macrophages) and differentiated MPRO 2.1 cells (promyelocytes/neutrophils). The results showed that despite a generation of reactive oxygen species, exposure to 20 nm citrate-coated AgNP was not associated with major oxidative damage, inflammatory responses, nor cytotoxicity. Nevertheless, and most importantly, pre-exposure to the AgNP for 24 h enhanced RAW 264.7 cell phagocytic ability as well as the release of inflammatory cytokine interleukin-6 in response to lipopolysaccharide (LPS). In MPRO 2.1 cells, AgNP pre-exposure also resulted in enhanced phagocytic ability; however, these cells manifest reduced cell degranulation (elastase release) and oxidative burst in response to phorbol myristate acetate (PMA). Taken together, these findings indicated to us that exposure to AgNP, despite not being directly (cyto)toxic to these cells, had the potential to alter immune cell responses. The findings underscore the import of assessing immune cell function post-exposure to ENM beyond the standard endpoints such as oxidative stress and cytotoxicity. In addition, these findings further illustrate the importance of understanding the underlying molecular mechanisms of ENM-cellular interactions, particularly in the immune system.http://dx.doi.org/10.1080/1547691X.2019.1588928nanotoxicologynanotoxicityimmunomodulationimmunotoxicityimmune activationsuppression
spellingShingle Nasser B. Alsaleh
Valerie C. Minarchick
Ryan P. Mendoza
Bipin Sharma
Ramakrishna Podila
Jared M. Brown
Silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in RAW 264.7 macrophages and MPRO 2.1 neutrophils
Journal of Immunotoxicology
nanotoxicology
nanotoxicity
immunomodulation
immunotoxicity
immune activation
suppression
title Silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in RAW 264.7 macrophages and MPRO 2.1 neutrophils
title_full Silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in RAW 264.7 macrophages and MPRO 2.1 neutrophils
title_fullStr Silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in RAW 264.7 macrophages and MPRO 2.1 neutrophils
title_full_unstemmed Silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in RAW 264.7 macrophages and MPRO 2.1 neutrophils
title_short Silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in RAW 264.7 macrophages and MPRO 2.1 neutrophils
title_sort silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in raw 264 7 macrophages and mpro 2 1 neutrophils
topic nanotoxicology
nanotoxicity
immunomodulation
immunotoxicity
immune activation
suppression
url http://dx.doi.org/10.1080/1547691X.2019.1588928
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