Evaluation of a simultaneous adsorption device for cytokines and platelet–neutrophil complexes in vitro and in a rabbit acute lung injury model

Abstract Background Platelet–neutrophil complexes (PNCs) readily migrate into tissues and induce tissue damage via cytokine or other pathogenic factors release. These actions are involved in onset and progression of acute respiratory distress syndrome (ARDS). Thus, simultaneous removal of cytokines and activated neutrophils, including PNCs by blood purification may prevent development of ARDS and enhance drug effects. The goal of this study was to examine the effect of a newly developed adsorption column (NOA-001) that eliminates cytokines and activated neutrophils in a lung injury model. Results Adsorption of cytokines, such as IL-8, IL-6 and HMGB-1, and PNCs was first measured in vitro. Lung injury was induced by HCl and lipopolysaccharide intratracheal infusion in rabbits ventilated at a low tidal volume (7–8 mL/kg) and PEEP (2.5 cmH2O) for lung protection. Arterial blood gas, hematologic values, plasma IL-8, blood pressure and heart rate were measured, and lung damage was evaluated histopathologically in animals treated with 8-h direct hemoperfusion with or without use of NOA-001. The in vitro adsorption rates for IL-8, IL-6, HMGB-1, activated granulocytes and PNCs were 99.5 (99.4–99.5)%, 63.9 (63.4–63.9)%, 57.6 (57.4–62.1)%, 9.9 (-4.4–21.3)% and 60.9 (49.0–67.6)%, respectively. Absorption of PNCs onto fibers was confirmed microscopically. These adsorption effects were associated with several improvements in the rabbit model. In respiratory function, the PaO2/FIO2 ratios at 8 h were 314 ± 55 mmHg in the NOA-001 group and 134 ± 41 mmHg in the sham group. The oxygenation index and PaCO2 at 8 h were 9.6 ± 3.1 and 57.0 ± 9.6 mmHg in the sham group and 3.0 ± 0.8 and 40.4 ± 4.5 mmHg in the NOA-001 group, respectively (p < 0.05). Blood pH at 8 h reached 7.18 ± 0.06 in the sham group, but was maintained at 7.36 ± 0.03 (within the normal range) in the NOA-001 group (p < 0.05). In lung histopathology, fewer hyaline membrane and inflammatory cells were observed in the NOA-001 group. Conclusion A column for simultaneous removal of cytokines and PNCs showed efficacy for improvement of pulmonary function in an animal model. This column may be effective in support of treatment of ARDS.

Download Full-text

Evaluation of A Simultaneous Adsorption Device For Cytokines And Neutrophil-Platelet Complexes In Vitro And In A Lung-Protective Ventilated Rabbit Acute Lung Injury Model

10.21203/rs.3.rs-558676/v1 ◽

2021 ◽

Author(s):

Yumiko Sekiya ◽

Kaoru Shimada ◽

Hiroshi Takahashi ◽

Chisa Kuga ◽

Shunsuke Komachi ◽

...

Keyword(s):

Lung Injury ◽

Sham Group ◽

Rabbit Model ◽

Oxygenation Index ◽

Lung Damage ◽

Simultaneous Removal ◽

Lung Protection ◽

Arterial Blood ◽

Activated Neutrophils

Abstract Background: Neutrophil-platelet complexes (NPCs) readily migrate into tissues and induce tissue damage via cytokine or other pathogenic factors release. These actions are involved in onset and progression of acute respiratory distress syndrome (ARDS). Thus, simultaneous removal of cytokines and activated neutrophils that includes NPCs by blood purification may prevent development of ARDS and enhance drug effects. The goal of this study was to examine the effect of a newly developed adsorption column (NOA-001) that eliminates cytokines and activated neutrophils in a lung injury model.Results: Adsorption of cytokines such as IL-8, IL-6 and HMGB-1, and NPCs was first measured in vitro. Lung injury was induced by HCl and lipopolysaccharide intratracheal infusion in rabbits ventilated at a low tidal volume (7-8 mL/kg) and PEEP (2.5 cmH2O) for lung protection. Arterial blood gas, hematologic values, plasma IL-8, blood pressure and heart rate were measured, and lung damage was evaluated histopathologically in animals treated with 8-hour direct hemoperfusion with or without use of NOA-001. The in vitro adsorption rates for IL-8, IL-6, HMGB-1, activated granulocytes and NPCs were 99.4 ± 0.0164%, 63.6 ± 0.367%, 59.0 ± 1.58%, 7.05 ± 9.63% and 55.7 ± 12.7%, respectively. Absorption of NPCs onto fibers was confirmed microscopically. These adsorption effects were associated with several improvements in the rabbit model. In respiratory function, the PaO2/FIO2 ratios at 8 h were 314 ± 55.3 mmHg in the NOA-001 group and 134 ± 40.8 mmHg in the sham group. The oxygenation index and PaCO2 also differed significantly between the two groups (p<0.05). Acidosis was observed in the sham group, whereas blood pH was maintained within the normal range in the NOA-001 group (p<0.05). In lung histopathology, fewer hyaline membrane and inflammatory cells were observed in the NOA-001 group.Conclusion: A column for simultaneous removal of cytokines and NPCs showed efficacy for improvement of pulmonary function in an animal model. This column may be effective in support of treatment of ARDS.

Download Full-text

Immunomodulation Properties of a Novel β-Glucan Extract from the Mushroom Lentinus Edodes in an In-Vitro Lung Injury Model

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a2114 ◽

2019 ◽

Author(s):

E.J. Murphy ◽

C. Masterson ◽

E. Rezoagli ◽

D. O'Toole ◽

J.G. Laffey ◽

...

Keyword(s):

Lung Injury ◽

Lentinus Edodes ◽

Injury Model ◽

Lung Injury Model

Download Full-text

Fas Ligand Released by Activated Monocytes Causes Apoptosis of Lung Epithelial Cells in Human Acute Lung Injury Model in Vitro

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.31.386 ◽

2008 ◽

Vol 31 (3) ◽

pp. 386-390 ◽

Cited By ~ 18

Author(s):

Mitsuhiko Mizuta ◽

Hiroo Nakajima ◽

Naruhiko Mizuta ◽

Yoshihiro Kitamura ◽

Yasufumi Nakajima ◽

...

Keyword(s):

Acute Lung Injury ◽

Epithelial Cells ◽

Lung Injury ◽

Fas Ligand ◽

Lung Epithelial Cells ◽

Injury Model ◽

Lung Epithelial ◽

Lung Injury Model ◽

Activated Monocytes

Download Full-text

33 CHANGES OF SURFACTANT IN VITRO FUNCTION IN A LONG TERM LUNG INJURY MODEL

Shock ◽

10.1097/00024382-199505000-00034 ◽

1995 ◽

Vol 3 (5) ◽

pp. 11

Author(s):

W. Strohmaier ◽

G. Schlag ◽

H. Redl

Keyword(s):

Lung Injury ◽

Injury Model ◽

Lung Injury Model

Download Full-text

Extracellular Matrix Remodeling Associated with Bleomycin-Induced Lung Injury Supports Pericyte-To-Myofibroblast Transition

10.1101/2020.11.16.384776 ◽

2020 ◽

Author(s):

Riley T. Hannan ◽

Andrew E. Miller ◽

Ruei-Chun Hung ◽

Catherine Sano ◽

Shayn M. Peirce ◽

...

Keyword(s):

Lung Injury ◽

Lineage Tracing ◽

Αvβ3 Integrin ◽

List Type ◽

Matrix Remodeling ◽

Injury Model ◽

Lung Injury Model ◽

Prior Literature ◽

The Many

AbstractOf the many origins of pulmonary myofibroblasts, microvascular pericytes are a known source. Prior literature has established the ability of pericytes to transition into myofibroblasts, but provide limited insight into molecular cues that drive this process during lung injury repair and fibrosis. Fibronectin and RGD-binding integrins have long been considered pro-fibrotic factors in myofibroblast biology, and here we test the hypothesis that these known myofibroblast cues coordinate pericyte-to-myofibroblast transitions. Specifically, we hypothesized that αvβ3 integrin engagement on fibronectin induces pericyte transition into myofibroblastic phenotypes in the murine bleomycin lung injury model. Myosin Heavy Chain 11 (Myh11)-CreERT2 lineage tracing in transgenic mice allows identification of cells of pericyte origin and provides a robust tool for isolating pericytes from tissues for further evaluation. We used this murine model to track and characterize pericyte behaviors during tissue repair. The majority of Myh11 lineage-positive cells are positive for the pericyte surface markers, PDGFRβ (55%) and CD146 (69%), and display typical pericyte morphology with spatial apposition to microvascular networks. After intratracheal bleomycin treatment of mice, Myh11 lineage-positive cells showed significantly increased contractile and secretory markers, as well as αv integrin expression. According to RNASeq measurements, many disease and tissue-remodeling genesets were upregulated in Myh11 lineage-positive cells in response to bleomycin-induced lung injury. In vitro, blocking αvβ3 binding through cyclo-RGDfK prevented expression of the myofibroblastic marker αSMA relative to controls. In response to RGD-containing provisional matrix proteins present in lung injury, pericytes may alter their integrin profile. This altered matrix-integrin axis contributes to pericyte-to-myofibroblastic transition and represents a possible therapeutic target for limiting the myofibroblastic burden in lung fibrosis.HighlightsPericyte lineage model enables study of transdifferentiating pericytesHigh dimensional flow cytometry used to characterize pulmonary stromal cellsPulmonary pericytes express matrix-remodeling genes and proteins in lung injuryMyofibroblasts derived from pericytes have active αvβ3 integrinIn vitro assay reveals necessity of RGD for pericyte transdifferentiation

Download Full-text

Pellino1 promoted inflammation in lung injury model of sepsis by TRAF6/ NF-κB signal pathway

Journal of Inflammation ◽

10.1186/s12950-021-00276-6 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Xiaqing Liu ◽

Zhengfang Lin ◽

Yufeng Xu

Keyword(s):

Lung Injury ◽

In Vitro Model ◽

Signal Pathway ◽

Male Mice ◽

Injury Model ◽

Lung Injury Model ◽

Mrna And Protein Expression ◽

Vitro Model

Abstract Background This study was designed to investigate the role of Pellino1 in lung injury model of sepsis and its anti-inflammation mechanism. Method: C57BL/6 male mice (6–7 weeks old) and Pellino1−/− male mice were subjected to laparotomy followed by extracorporeal cecum mobilization and ligation. THP-1 cells were treated with 500 ng/ml of LPS for 4 h. Both mRNA and protein expression of Pellino1 was increased at time dependence in lung tissue of lung injury model of sepsis mice. Knockout of Pellino1 attenuated lung injury and inhibited inflammation of sepsis mice. While Pellino1 protein enhanced lung injury and increased inflammation of sepsis mice. Pellino1 promoted inflammation in in vitro model of lung injury by TRAF6/ NF-κB signal pathway. Result TRAF6 inhibitor attenuated the effects of Pellino1 on inflammation and lung injury in mice of sepsis. Similarly, NF-κB inhibitor also suppressed the effects of Pellino1 on inflammation and lung injury in mice of sepsis. The activation of TRAF6 or induction of NF-κB attenuated the effects of Pellino1 on inflammation in in vitro model of sepsis. The inhibition of TRAF6 or suppression of NF-κB reduced the effects of Pellino1 on inflammation in in vitro model of sepsis. Conclusions These results suggested that Pellino1 promoted inflammation in lung injury model of sepsis by TRAF6/ NF-κB signal pathway.

Download Full-text

Dynamic single-slice CT estimates whole-lung dual-energy CT variables in pigs with and without experimental lung injury

Intensive Care Medicine Experimental ◽

10.1186/s40635-019-0273-y ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 1

Author(s):

John N. Cronin ◽

João Batista Borges ◽

Douglas C. Crockett ◽

Andrew D. Farmery ◽

Göran Hedenstierna ◽

...

Keyword(s):

Lung Injury ◽

Dual Energy ◽

Dual Energy Ct ◽

Lung Density ◽

Density Distributions ◽

Single Slice ◽

Injury Model ◽

Lung Injury Model ◽

Ct Density ◽

Surfactant Depletion

Abstract Background Dynamic single-slice CT (dCT) is increasingly used to examine the intra-tidal, physiological variation in aeration and lung density in experimental lung injury. The ability of dCT to predict whole-lung values is unclear, especially for dual-energy CT (DECT) variables. Additionally, the effect of inspiration-related lung movement on CT variables has not yet been quantified. Methods Eight domestic pigs were studied under general anaesthesia, including four following saline-lavage surfactant depletion (lung injury model). DECT, dCT and whole-lung images were collected at 12 ventilatory settings. Whole-lung single energy scans images were collected during expiratory and inspiratory apnoeas at positive end-expiratory pressures from 0 to 20 cmH2O. Means and distributions of CT variables were calculated for both dCT and whole-lung images. The cranio-caudal displacement of the anatomical slice was measured from whole-lung images. Results Mean CT density and volume fractions of soft tissue, gas, iodinated blood, atelectasis, poor aeration, normal aeration and overdistension correlated between dCT and the whole lung (r2 0.75–0.94) with agreement between CT density distributions (r 0.89–0.97). Inspiration increased the matching between dCT and whole-lung values and was associated with a movement of 32% (SD 15%) of the imaged slice out of the scanner field-of-view. This effect introduced an artefactual increase in dCT mean CT density during inspiration, opposite to that caused by the underlying physiology. Conclusions Overall, dCT closely approximates whole-lung aeration and density. This approximation is improved by inspiration where a decrease in CT density and atelectasis can be interpreted as physiological rather than artefactual.

Download Full-text