Expression of von Willebrand factor, pulmonary intravascular macrophages, and Toll-like receptors in lungs of septic foals

Harrison, Jacqueline M. E.; Quanstrom, Leah M.; Robinson, Alex R.; Wobeser, Bruce; Anderson, Stacy; Singh, Baljit

doi:10.4142/jvs.2017.18.1.17

Cited by 4 publications

(4 citation statements)

References 30 publications

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“…Therefore, in our studies we demonstrated disrupted endothelial barrier on NPs and PHMG exposure, whereas with FL treatment we observed an increase in CD31 (or Pecam) expression signifying an onset of the barrier recovery process. Moreover, increased vWF levels was observed on exposure to PHMG on-chip which is in line with current research findings confirming that elevated vWF amount is associated with inflammation and emphysema pathogenesis (Harrison et al, 2017;Langholm et al, 2020). It signifies that apical epithelial exposure of the NPs and toxic PHMG were able to induce a much deeper basal effect inciting endothelial activation and damage in our cellular models on-chip.…”

Section: Discussionsupporting

confidence: 91%

A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip

et al. 2023

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Prolonged exposure to environmental respirable toxicants can lead to the development and worsening of severe respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and fibrosis. The limited number of FDA-approved inhaled drugs for these serious lung conditions has led to a shift from in vivo towards the use of alternative in vitro human-relevant models to better predict the toxicity of inhaled particles in preclinical research. While there are several inhalation exposure models for the upper airways, the fragile and dynamic nature of the alveolar microenvironment has limited the development of reproducible exposure models for the distal lung. Here, we present a mechanistic approach using a new generation of exposure systems, the Cloud α AX12. This novel in vitro inhalation tool consists of a cloud-based exposure chamber (VITROCELL) that integrates the breathing AXLung-on-chip system (AlveoliX). The ultrathin and porous membrane of the AX12 plate was used to create a complex multicellular model that enables key physiological culture conditions: the air-liquid interface (ALI) and the three-dimensional cyclic stretch (CS). Human-relevant cellular models were established for a) the distal alveolar-capillary interface using primary cell-derived immortalized alveolar epithelial cells (AXiAECs), macrophages (THP-1) and endothelial (HLMVEC) cells, and b) the upper-airways using Calu3 cells. Primary human alveolar epithelial cells (AXhAEpCs) were used to validate the toxicity results obtained from the immortalized cell lines. To mimic in vivo relevant aerosol exposures with the Cloud α AX12, three different models were established using: a) titanium dioxide (TiO2) and zinc oxide nanoparticles b) polyhexamethylene guanidine a toxic chemical and c) an anti-inflammatory inhaled corticosteroid, fluticasone propionate (FL). Our results suggest an important synergistic effect on the air-blood barrier sensitivity, cytotoxicity and inflammation, when air-liquid interface and cyclic stretch culture conditions are combined. To the best of our knowledge, this is the first time that an in vitro inhalation exposure system for the distal lung has been described with a breathing lung-on-chip technology. The Cloud α AX12 model thus represents a state-of-the-art pre-clinical tool to study inhalation toxicity risks, drug safety and efficacy.

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Section: Discussionsupporting

confidence: 91%

A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip

et al. 2023

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“…As PIMs are capable of directly responding to inflammatory stimuli within both the airway and intravascular compartments, they have a unique role in pulmonary immunity, perhaps explaining the recognised susceptibility of the horse to endotoxaemia 150 . Recently, Harrison et al 198 reported an increased expression of inflammatory molecules, such as TLR4 and TLR9, in mononuclear cells in the lungs of septic foals, potentially including PIMs (see Figure 3). This group also reported an increase in PIMs from foals that died from sepsis, compared to healthy animals.…”

Section: The Mononuclear Phagocyte System Of the Horsementioning

confidence: 99%

The equine mononuclear phagocyte system: The relevance of the horse as a model for understanding human innate immunity

Karagianni

Lisowski

Hume

et al. 2020

Equine Veterinary Journal

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Horses are already recognised as models for several human diseases, including metabolic syndrome, asthma, musculoskeletal diseases, melanoma and autoimmune uveitis. 1-6 More than 100 equine hereditable conditions may serve as models for human disorders, including inflammation, muscular or fertility disorders, osteoarthritis and even depression. 7-10 The horse has the potential to represent an appropriate

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“…Horses are susceptible to many respiratory diseases which cause major economic and personal losses to the horse industry [ 1 ]. Diseases such as endotoxin-induced lung injury, recurrent airway disease and infectious diseases such as Rhodococcus equi cause lung inflammation which underlies clinical signs of respiratory diseases [ 2 ]. The role of various cells such as macrophages and neutrophils and immune molecules such as Toll-like receptors is under active investigation [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Diseases such as endotoxin-induced lung injury, recurrent airway disease and infectious diseases such as Rhodococcus equi cause lung inflammation which underlies clinical signs of respiratory diseases [ 2 ]. The role of various cells such as macrophages and neutrophils and immune molecules such as Toll-like receptors is under active investigation [ 2 , 3 ]. The advances made so far have created a better understanding of the mechanisms of respiratory diseases of the horse; however, much remains to be revealed.…”

Section: Introductionmentioning

confidence: 99%

Research article expression of surfactant protein-A and D, and CD9 in lungs of 1 and 30 day old foals

et al. 2021

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Background Respiratory diseases are a major cause of morbidity and mortality in the horses of all ages including foals. There is limited understanding of the expression of immune molecules such as tetraspanins and surfactant proteins (SP) and the regulation of the immune responses in the lungs of the foals. Therefore, the expression of CD9, SP-A and SP-D in foal lungs was examined. Results Lungs from one day old (n = 6) and 30 days old (n = 5) foals were examined for the expression of CD9, SP-A, and SP-D with immunohistology and Western blots. Western blot data showed significant increase in the amount of CD9 protein (p = 0.0397) but not of SP-A and SP-D at 30 days of age compared to one day. Immunohistology detected CD9 in the alveolar septa and vascular endothelium but not the bronchiolar epithelium in the lungs of the foals in both age groups. SP-A and SP-D expression was localized throughout the alveolar septa including type II alveolar epithelial cells and the vascular endothelium of the lungs in all the foals. Compared to one day old foals, the expression of SP-A and SP-D appeared to be increased in the bronchiolar epithelium of 30 day old foals. Pulmonary intravascular macrophages were also positive for SP-A and SP-D in 30 days old foals and these cells are not developed in the day old foals. Conclusions This is the first data on the expression of CD9, SP-A and SP-D in the lungs of foals.

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Expression of von Willebrand factor, pulmonary intravascular macrophages, and Toll-like receptors in lungs of septic foals

Cited by 4 publications

References 30 publications

A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip

A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip

The equine mononuclear phagocyte system: The relevance of the horse as a model for understanding human innate immunity

Research article expression of surfactant protein-A and D, and CD9 in lungs of 1 and 30 day old foals

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