Role of necroptosis of alveolar macrophages in acute lung inflammation of mice exposed to titanium dioxide nanoparticles

Sagawa, Takahiro; Honda, Akira; Ishikawa, Raga; Miyasaka, Natsuko; Nagao, Megumi; Akaji, Sakiko; Kida, Takashi; Tsujikawa, Takahiro; Yoshida, Tatsushi; Kawahito, Yutaka; Takano, Hirohisa

doi:10.1080/17435390.2021.2022231

Cited by 15 publications

(11 citation statements)

References 64 publications

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“…There was strong colocalization between the necroptosis-related markers, p-MLKL, and the markers of macrophages, CD68 and F4/80. In agreement with our results, several recently published studies also demonstrated that macrophage necroptosis was involved as part of the mechanism of enhancing inflammatory responses ( 21 – 23 ).…”

Section: Discussionsupporting

confidence: 93%

Enterococcus faecalis -Induced Macrophage Necroptosis Promotes Refractory Apical Periodontitis

Dai

Jiang

et al. 2022

Microbiol Spectr

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Section: Discussionsupporting

confidence: 93%

Enterococcus faecalis -Induced Macrophage Necroptosis Promotes Refractory Apical Periodontitis

Dai

Jiang

et al. 2022

Microbiol Spectr

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“…Current literature primarily focuses on the most prominent phase of the immune responses, i.e. at the response peak which occurs at least several hours after application triggered by the respective NPs ( 76–79 ). Here, we delved into the intricate molecular events of sterile particle-triggered vascular inflammation in the lungs, focusing on the initial steps and mechanisms of neutrophil involvement.…”

Section: Discussionmentioning

confidence: 99%

eATP/P2X7R axis drives nanoparticle induced neutrophil recruitment in the pulmonary microcirculation

Li,

Liu,

Han

et al. 2024

Preprint

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Exposure to nanoparticles (NPs) is frequently associated with adverse cardiovascular effects. In contrast, NPs in nanomedicine hold great promise for precise lung-specific drug delivery, especially considering the extensive pulmonary capillary network that facilitates interactions with bloodstream-suspended particles. Therefore, exact knowledge about interactions and effects of engineered NPs with the pulmonary microcirculation are instrumental for future application of this technology in patients. To unravel the real-time dynamics of intravenously delivered NPs and their effects in the pulmonary microvasculature, we employed intravital microscopy of the mouse lung. PEG amine-modified quantum dots (aQDs) with a low potential for biomolecule and cell interactions and carboxyl-modified quantum dots (cQDs) with a high interaction potential were used, representing two different NP subtypes. Only aQDs triggered rapid neutrophil recruitment in microvessels and their subsequent recruitment to the alveolar space. Application of specific inhibitors revealed that the aQDs induced neutrophil recruitment was linked to cellular degranulation, TNF-α, and DAMP release into the circulation, particularly extracellular ATP (eATP). Stimulation of the ATP-gated P2X7R induced the expression of E-selectin on microvascular endothelium with the subsequent E-selectin depended neutrophilic immune response. Leukocyte integrins (LFA-1 and MAC-1) mediated adhesion and reduction in neutrophil crawling velocity on the vascular surface. In summary, this study unravels the complex cascade of neutrophil recruitment during NP-induced sterile inflammation. Thereby we demonstrate novel adverse effects for NPs in the pulmonary microcirculation and provide critical insights for optimizing NP-based drug delivery and therapeutic intervention strategies, to ensure their efficacy and safety in clinical applications.

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“…Raman spectroscopy is rapidly emerging in the biological field because it can identify materials with minimal invasion without the need for labels. 11,12 This feature makes it possible to apply Raman spectroscopy to living materials such as cells and tissues as well as inorganic or organic materials. 13,14 On the other hand, tissue slides treated with HE staining or immunostaining have strong autofluorescence, which competes with Raman signals, leading to a major issue.…”

Section: Discussionmentioning

confidence: 99%

Post-staining Raman analysis of histological sections following decolorization

Akaji

Sagawa

Honda

et al. 2022

Analyst

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Role of necroptosis of alveolar macrophages in acute lung inflammation of mice exposed to titanium dioxide nanoparticles

Cited by 15 publications

References 64 publications

Enterococcus faecalis -Induced Macrophage Necroptosis Promotes Refractory Apical Periodontitis

Enterococcus faecalis -Induced Macrophage Necroptosis Promotes Refractory Apical Periodontitis

eATP/P2X7R axis drives nanoparticle induced neutrophil recruitment in the pulmonary microcirculation

Post-staining Raman analysis of histological sections following decolorization

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