Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using ourin vivoexperimental model. First, we exhibit the effects of nanoparticles on pulmonary inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS) as a disease model in innate immunity, and demonstrate that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Second, we introduce the effects of nanoparticles on allergic pulmonary inflammation as a disease model in adaptive immunity, and show that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic inflammation, including adjuvant effects on Th2-milieu. Third, we show that very small nanoparticle exposure exacerbates emphysematous pulmonary inflammation, which is concomitant with enhanced lung expression of proinflammatory molecules (including those that are innate immunity related). Taken together, nanoparticle exposure may synergistically facilitate pathological pulmonary inflammation via both innate and adaptive immunological impairment.

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Facilitating Effects of Nanoparticles/Materials on Sensitive Immune-Related Lung Disorders

Journal of Nanomaterials ◽

10.1155/2011/407402 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Ken-ichiro Inoue ◽

Hirohisa Takano

Keyword(s):

Lung Inflammation ◽

Disease Model ◽

Allergic Airway Inflammation ◽

Pulmonary Exposure ◽

Adverse Health Effects ◽

Inflammatory Conditions ◽

Pathological Conditions ◽

Adjuvant Effects ◽

Immunological Abnormalities

Although the adverse health effects of nanoparticles/materials have been proposed and are being clarified, their facilitating effects on preexisting pathological conditions have not been fully examined. In this paper, we provide insights into the immunotoxicity of nanoparticles/materials as an aggravating factor in hypersusceptible subjects, especially those with immune-related respiratory disorders using ourin vivoexperimental model. We first exhibit the effects of nanoparticles/materials on lung inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS)in vivoas a disease model in innate immunity, and demonstrated that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Secondly, we introduce the effects of nanoparticles/materials on allergic asthmain vivoas a disease model in adaptive immunity, and showed that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic airway inflammation, including adjuvant effects on Th2-milieu. Taken together, nanoparticle exposure may synergistically facilitate pathological inflammatory conditions in the lung via both innate and adaptive immunological abnormalities.

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Differential Effects of Nano TiO2 and CeO2 on Normal Human Lung Epithelial Cells In Vitro

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2019.16737 ◽

2019 ◽

Vol 19 (11) ◽

pp. 6907-6923 ◽

Cited By ~ 1

Author(s):

Sheau-Fung Thai ◽

Carlton P. Jones ◽

Garret B. Nelson ◽

Beena Vallanat ◽

Micaela Killius ◽

...

Keyword(s):

Signaling Pathways ◽

Cell Model ◽

Engineered Nanoparticles ◽

Protein Adducts ◽

Lung Epithelial Cells ◽

Adverse Health Effects ◽

Normal Human ◽

Respiratory Epithelial

Nano-TiO2 and nano-CeO2 are among the most widely used engineered nanoparticles (NPs). We investigated a variety of endpoints to assess the toxicity of eight of these NPs to induce potentially adverse health effects in an In Vitro human respiratory epithelial cell model. These endpoints include cytotoxicity, reactive oxygen species (ROS)/reactive nitrogen species (RNS) production, 8-hydroxy-2_-deoxyguanosine (8-oxo-dG), endogenous DNA adducts, Apurinic/apyrimidinic (AP) sites, 4-Hrdoxynonenal (4-HNE) protein adducts, Malondialdehyde (MDA) protein adducts, and genomics analysis on altered signaling pathways. Our results indicated that cytotoxicity assays are relatively insensitive, and we detected changes in other endpoints at concentrations much lower than those inducing cytotoxicity. Among the ROS-related endpoints, 8-oxo-dG is relatively more sensitive than other assays, and nano-TiO2 induced more 8-oxo-dG formation than nano-CeO2. Finally, there are many signaling pathways changes at concentrations at which no cytotoxicity was observed. These alterations in signaling pathways correlated well with In Vitro toxicity that was observed at higher concentrations, and with in vivo adverse outcome pathways caused by nano-TiO2 and nano-CeO2 in experimental animals.

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Collectin Kidney 1 Plays an Important Role in Innate Immunity against Streptococcus pneumoniae Infection

Journal of Innate Immunity ◽

10.1159/000453316 ◽

2017 ◽

Vol 9 (2) ◽

pp. 217-228 ◽

Cited By ~ 7

Author(s):

Insu Hwang ◽

Kenichiro Mori ◽

Katsuki Ohtani ◽

Yasuyuki Matsuda ◽

Nitai Roy ◽

...

Keyword(s):

Innate Immunity ◽

Streptococcus Pneumoniae ◽

Pulmonary Inflammation ◽

Dependent Manner ◽

Complement Pathway ◽

Calcium Dependent ◽

Host Protection ◽

In The Wild

Collectins are C-type lectins that are involved in innate immunity as pattern recognition molecules. Recently, collectin kidney 1 (CL-K1) has been discovered, and in vitro studies have shown that CL-K1 binds to microbes and activates the lectin complement pathway. However, in vivo functions of CL-K1 against microbes have not been elucidated. To investigate the biological functions of CL-K1, we generated CL-K1 knockout (CL-K1-/-) mice and then performed a Streptococcus pneumoniae infection analysis. First, we found that recombinant human CL-K1 bound to S. pneumoniae in a calcium-dependent manner, and induced complement activation. CL-K1-/- mice sera formed less C3 deposition on S. pneumoniae. Furthermore, immunofluorescence analysis in the wild-type (WT) mice demonstrated that CL-K1 and C3 were localized on S. pneumoniae in infected lungs. CL-K1-/- mice revealed decreased phagocytosis of S. pneumoniae. Consequently, less S. pneumoniae clearance was observed in their lungs. CL-K1-/- mice showed severe pulmonary inflammation and weight loss in comparison with WT mice. Finally, the decreased clearance and severe pulmonary inflammation caused by S. pneumoniae infection might cause higher CL-K1-/- mice lethality. Our results suggest that CL-K1 might play an important role in host protection against S. pneumoniae infection through the activation of the lectin complement pathway.

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Acute vaping exacerbates microbial pneumonia due to calcium (Ca2+) dysregulation

PLoS ONE ◽

10.1371/journal.pone.0256166 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0256166

Author(s):

Rui Zhang ◽

Myles M. Jones ◽

De’Jana Parker ◽

Ronna E. Dornsife ◽

Nathan Wymer ◽

...

Keyword(s):

Pulmonary Inflammation ◽

Airway Epithelial Cells ◽

Lung Pathology ◽

Airway Epithelial ◽

Microbial Infection ◽

Inflammatory Cytokine Production ◽

Pulmonary Exposure ◽

Lung Histology ◽

Macrophage Chemotaxis

As electronic cigarette (E-cig) use, also known as “vaping”, has rapidly increased in popularity, data regarding potential pathologic effects are recently emerging. Recent associations between vaping and lung pathology have led to an increased need to scrutinize E-cigs for adverse health impacts. Our previous work (and others) has associated vaping with Ca2+-dependent cytotoxicity in cultured human airway epithelial cells. Herein, we develop a vaped e-liquid pulmonary exposure mouse model to evaluate vaping effects in vivo. Using this model, we demonstrate lung pathology through the use of preclinical measures, that is, the lung wet: dry ratio and lung histology/H&E staining. Further, we demonstrate that acute vaping increases macrophage chemotaxis, which was ascertained using flow cytometry-based techniques, and inflammatory cytokine production, via Luminex analysis, through a Ca2+-dependent mechanism. This increase in macrophage activation appears to exacerbate pulmonary pathology resulting from microbial infection. Importantly, modulating Ca2+ signaling may present a therapeutic direction for treatment against vaping-associated pulmonary inflammation.

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Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates for triple-negative breast cancer treatment

10.31234/osf.io/zhpa4 ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Triple Negative ◽

Growth Factor Receptor ◽

Engineered Nanoparticles ◽

Efficacy Evaluation ◽

Dual Action ◽

Epidermal Growth ◽

Laminin 411 ◽

Immunologic Analysis

Engineered nanoparticles are widely used for delivery of drugs but frequently lack proof of safetyfor cancer patient's treatment. All-in-one covalent nanodrugs of the third generation have beensynthesized based on a poly(β-L-malic acid) (PMLA) platform, targeting human triple-negativebreast cancer (TNBC). They significantly inhibited tumor growth in nude mice by blockingsynthesis of epidermal growth factor receptor, and α4 and β1 chains of laminin-411, the tumorvascular wall protein and angiogenesis marker. PMLA and nanodrug biocompatibility and toxicityat low and high dosages were evaluated in vitro and in vivo. The dual-action nanodrug and singleactionprecursor nanoconjugates were assessed under in vitro conditions and in vivo with multipletreatment regimens (6 and 12 treatments). The monitoring of TNBC treatment in vivo withdifferent drugs included blood hematologic and immunologic analysis after multiple intravenousadministrations. The present study demonstrates that the dual-action nanoconju-gate is highlyeffective in preclinical TNBC treatment without side effects, supported by hematologic andimmunologic assays data. PMLA-based nanodrugs of the Polycefin™ family passed multipletoxicity and efficacy tests in vitro and in vivo on preclinical level and may prove to be optimizedand efficacious for the treatment of cancer patients in the future.

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Faculty Opinions recommendation of Near-infrared fluorescent sensor for in vivo copper imaging in a murine Wilson disease model.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13931984.15387095 ◽

2012 ◽

Author(s):

Janet Morrow

Keyword(s):

Wilson Disease ◽

Near Infrared ◽

Fluorescent Sensor ◽

Disease Model

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Selective deletion of SHIP-1 in hematopoietic cells in mice leads to severe lung inflammation involving ILC2 cells

Scientific Reports ◽

10.1038/s41598-021-88677-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xujun Ye ◽

Fengrui Zhang ◽

Li Zhou ◽

Yadong Wei ◽

Li Zhang ◽

...

Keyword(s):

Lung Inflammation ◽

Airway Remodeling ◽

Pulmonary Inflammation ◽

Hematopoietic Cells ◽

Cell Lineage ◽

Allergic Inflammation ◽

Cell Types ◽

Lymphoid Cells ◽

Whole Body

AbstractSrc homology 2 domain–containing inositol 5-phosphatase 1 (SHIP-1) regulates the intracellular levels of phosphotidylinositol-3, 4, 5-trisphosphate, a phosphoinositide 3–kinase (PI3K) product. Emerging evidence suggests that the PI3K pathway is involved in allergic inflammation in the lung. Germline or induced whole-body deletion of SHIP-1 in mice led to spontaneous type 2-dominated pulmonary inflammation, demonstrating that SHIP-1 is essential for lung homeostasis. However, the mechanisms by which SHIP-1 regulates lung inflammation and the responsible cell types are still unclear. Deletion of SHIP-1 selectively in B cells, T cells, dendritic cells (DC) or macrophages did not lead to spontaneous allergic inflammation in mice, suggesting that innate immune cells, particularly group 2 innate lymphoid cells (ILC2 cells) may play an important role in this process. We tested this idea using mice with deletion of SHIP-1 in the hematopoietic cell lineage and examined the changes in ILC2 cells. Conditional deletion of SHIP-1 in hematopoietic cells in Tek-Cre/SHIP-1 mice resulted in spontaneous pulmonary inflammation with features of type 2 immune responses and airway remodeling like those seen in mice with global deletion of SHIP-1. Furthermore, when compared to wild-type control mice, Tek-Cre/SHIP-1 mice displayed a significant increase in the number of IL-5/IL-13 producing ILC2 cells in the lung at baseline and after stimulation by allergen Papain. These findings provide some hints that PI3K signaling may play a role in ILC2 cell development at baseline and in response to allergen stimulation. SHIP-1 is required for maintaining lung homeostasis potentially by restraining ILC2 cells and type 2 inflammation.

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T cell mediated hypersensitivity to previously tolerated iodinated contrast media precipitated by introduction of atezolizumab

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002521 ◽

2021 ◽

Vol 9 (5) ◽

pp. e002521

Author(s):

Sean Hammond ◽

Anna Olsson-Brown ◽

Joshua Gardner ◽

Paul Thomson ◽

Serat-E Ali ◽

...

Keyword(s):

Contrast Media ◽

Adverse Reactions ◽

Stevens Johnson Syndrome ◽

Iodinated Contrast ◽

Immune Mediated ◽

Johnson Syndrome ◽

Healthy Donors ◽

Concomitant Medications

Many adverse reactions associated with immune checkpoint inhibitor (ICI) treatments are immunologically driven and may necessitate discontinuation of the ICI. Herein, we present a patient who had been administered the radio contrast media amidotrizoate multiple times without issue but who then developed a Stevens-Johnson syndrome reaction after coadministration of atezolizumab. Causality was confirmed by a positive re-challenge with amidotrizoate and laboratory investigations that implicated T cells. Importantly, the introduction of atezolizumab appears to have altered the immunologic response to amidotrizoate in terms of the tolerance–elicitation continuum. Proof of concept studies demonstrated enhancement of recall responses to a surrogate antigen panel following in-vitro (healthy donors) and in-vivo (ICI patients) administrations of ICIs. Our findings highlight the importance of considering all concomitant medications in patients on ICIs who develop immune-mediated adverse reactions. In the event of some immune-related adverse reactions, it may be critical to identify the culprit antigen-forming entity that the ICIs have altered the perception of rather than simply attribute causality to the ICI itself in order to optimize both patient safety and treatment of malignancies.

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