Mechanistic insights into silica nanoparticle–allergen interactions on antigen presenting cell function in the context of allergic reactions

Johnson, Litty; Aglas, Lorenz; Punz, Benjamin; Dang, Hieu-Hoa; Christ, Constantin; Pointner, Lisa; Wenger, Mario; Hofstätter, Norbert; Hofer, Sabine; Geppert, Mark; Andosch, Ancuela; Ferreira, Fátima; Horejs‐Hoeck, Jutta; Duschl, Albert; Himly, Martin

doi:10.1039/d2nr05181h

Cited by 7 publications

(5 citation statements)

References 74 publications

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“…Birch pollen extract was prepared based on the protocol in Johnson et al with slight modifications [ 43 ]. In total, 100 mg of Betula pendula pollen was dispersed in 1 mL of DPBS.…”

Section: Methodsmentioning

confidence: 99%

“…Due to interferences of BPE with the LAL assay, a cell-based assay was employed for the endotoxin quantification in the obtained SN. HEK-Blue™-hTLR4 cells were used for endotoxin quantification in BPE, based on a protocol provided by Johnson et al [ 43 ] with slight modifications. The cells were cultured in DMEM supplemented with penicillin-streptomycin, glutamine, normocin, inactivated FBS and HEK-Blue™ Selection.…”

Section: Methodsmentioning

confidence: 99%

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Recovering What Matters: High Protein Recovery after Endotoxin Removal from LPS-Contaminated Formulations Using Novel Anti-Lipid A Antibody Microparticle Conjugates

Casonato Melo,

Fux,

Himly

et al. 2023

IJMS

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Endotoxins or lipopolysaccharides (LPS), found in the outer membrane of Gram-negative bacterial cell walls, can stimulate the human innate immune system, leading to life-threatening symptoms. Therefore, regulatory limits for endotoxin content apply to injectable pharmaceuticals, and excess LPS must be removed before commercialization. The majority of available endotoxin removal systems are based on the non-specific adsorption of LPS to charged and/or hydrophobic surfaces. Albeit effective to remove endotoxins, the lack of specificity can result in the unwanted loss of essential proteins from the pharmaceutical formulation. In this work, we developed microparticles conjugated to anti-Lipid A antibodies for selective endotoxin removal. Anti-Lipid A particles were characterized using flow cytometry and microscopy techniques. These particles exhibited a depletion capacity > 6 ×103 endotoxin units/mg particles from water, as determined with two independent methods (Limulus Amebocyte Lysate test and nanoparticle tracking analysis). Additionally, we compared these particles with a non-specific endotoxin removal system in a series of formulations of increasing complexity: bovine serum albumin in water < insulin in buffer < birch pollen extracts. We demonstrated that the specific anti-Lipid A particles show a higher protein recovery without compromising their endotoxin removal capacity. Consequently, we believe that the specificity layer integrated by the anti-Lipid A antibody could be advantageous to enhance product yield.

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“…Birch pollen extract was prepared based on the protocol in Johnson et al with slight modifications [ 43 ]. In total, 100 mg of Betula pendula pollen was dispersed in 1 mL of DPBS.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Recovering What Matters: High Protein Recovery after Endotoxin Removal from LPS-Contaminated Formulations Using Novel Anti-Lipid A Antibody Microparticle Conjugates

Casonato Melo,

Fux,

Himly

et al. 2023

IJMS

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“…Figure 9 illustrates the comprehensive experimental workflow overarching several immunotoxicity studies highlighting the different routes chosen for these studies, starting with the synthesis, surface functionalisation, and physico-chemical characterisation of the nanomaterials, the bionano interaction studies, and the determination of different biological / immunological endpoints. 27 [48], Mills-Goodlet et al [49], Johnson et al [50], and Punz et. al.…”

Section: Showcasing Complex Workflows In Human Immunotoxicity Assessm...mentioning

confidence: 99%

“…The sections concerning the biological and immunological readouts, as well pharmacological efficacy, independently expanded upon Section A. The focus in Figure 9B was on the mechanistic studies following uptake and presentation by professional antigen-presenting cell (APC) models using unmodified SiO2 nanomaterials [50] vs. differently surface functionalized particles [51]. As a model for APCs, monocyte-derived dendritic cells were generated from human whole blood samples as a preliminary step, again building a BIODA-type of reporting structure following SOPs.…”

Section: Showcasing Complex Workflows In Human Immunotoxicity Assessm...mentioning

confidence: 99%

Instance maps as an organising concept for complex experimental workflows as demonstrated for (nano)material safety research

Punz,

Brajnik,

Dokler

et al. 2024

Preprint

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Nanosafety assessment, which seeks to evaluate the risks from exposure to nanoscale materials, spans materials synthesis and characterisation, exposure science, toxicology, and computational approaches, resulting in complex experimental workflows and diverse data types. Managing the data flows, with a focus on provenance (who generated the data, for what purpose) and quality (how the data was generated, using which protocol, with which controls), as part of good research output management, is necessary to maximise the re-use potential and value of the data. The concept of Instance Maps has been developed and evolved to visualise experimental nanosafety workflows and to bridge the gap between the theoretical principles of FAIR (Findable, Accessible, Interoperable and Re-usable) data and the everyday practice of experimental researchers. While Instance Maps can be created for completed studies or publications, they are most effective when applied at the study design stage to associate the workflow with the nanomaterials, environmental conditions, method descriptions, protocols, biological and computational models to be used and the data flows arising from study execution. Application of the Instance Map Tool (described herein) to research workflows of increasing complexity is presented to demonstrate its utility, starting from assessment of nanomaterials transformations in complex media, and documentation of nanomaterial synthesis, functionalisation and characterisation, to description of the culturing of ecotoxicity model organisms Daphnia magna and their use in acute and chronic standardised tests for nanomaterials ecotoxicity assessment, and visualisation of complex workflows in human immunotoxicity assessment using cell lines and primary cellular models. These examples showcase the use of the Instance Map approach for coordination of materials and data flows in complex multi-partner collaborative projects, and to support demonstration case studies. Finally, areas for future development of the Instance Map approach and tool are highlighted.

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“…There is so far no indication that nanomaterials can be true allergens (Himly et al, 2017), however, their presence may affect the sensitization process, and the degree or duration of exposure. Uptake into and processing in antigenpresenting cells is essential for loading allergen-derived peptides into the MHC-II complex, and specific nanomaterials can affect these processes (Joubert et al, 2020;Johnson et al, 2023). Thus, co-exposure to nanomaterials and allergens may have direct effects on Th2-driven adaptive immune responses.…”

Section: Immune Response To Exposure: Role Of Cell Death and Alarm Si...mentioning

confidence: 99%

Editorial: Exploring impacts of combined exposures to particles and chemicals on immune reactions across living organisms

Boraschi

Duschl²,

Lynch³

et al. 2023

Front. Toxicol.

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Editorial on the Research TopicExploring impacts of combined exposures to particles and chemicals on immune reactions across living organisms 1 EditorialThe immune system of all living organisms has developed in order to preserve the integrity and functionality of the organism in the face of external invaders such as viruses, bacteria or pollutants. This encompasses a homeostatic role of patrolling and controlling the body tissues and organs, and a defensive role to face an external environment filled with microorganisms, particles and molecules of different nature, block the entry of potential threats and adapt to changes in the environment (Murphy et al., 2022). History of exposurePollutants of different origins and nature can have an impact on immunity (e.g., Glencross et al., 2020). Alterations in immune responses caused by air and water pollutants can hamper human and environmental health, both in terms of inadequate reactivity (immunosuppression, increased susceptibility to infections and diseases) and in terms of excessive response (pathological inflammation, allergies, autoimmunity) (e.g., Reinmuth-Selzle et al., 2017). The recent concept of the exposome, the measure of all exposures experienced by individuals through their lifetime (Rappaport, 2011), fully applies to the interaction between pollutants and immunity, since the immune system has a memory

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Mechanistic insights into silica nanoparticle–allergen interactions on antigen presenting cell function in the context of allergic reactions

Abstract: Impact of SiO2 NP-allergen interaction on dendritic cell function altering the immune response, eventually resulting in a harmless, beneficial outcome in terms of allergic reactivity.

Cited by 7 publications

References 74 publications

Recovering What Matters: High Protein Recovery after Endotoxin Removal from LPS-Contaminated Formulations Using Novel Anti-Lipid A Antibody Microparticle Conjugates

Recovering What Matters: High Protein Recovery after Endotoxin Removal from LPS-Contaminated Formulations Using Novel Anti-Lipid A Antibody Microparticle Conjugates

Instance maps as an organising concept for complex experimental workflows as demonstrated for (nano)material safety research

Editorial: Exploring impacts of combined exposures to particles and chemicals on immune reactions across living organisms

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