Perfluorochemical liquids modulate cell-mediated inflammatory responses

Nakstad, Britt; Wolfson, Marla R.; Shaffer, Thomas H.; Kähler, Hanne; Lindemann, Rolf; Fugelseth, Drude; Lyberg, Torstein

doi:10.1097/00003246-200109000-00013

Cited by 29 publications

(29 citation statements)

References 32 publications

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“…Thereby, Obraztsov and co-workers (24) noted a linear relationship between the magnitude of inhibition and the lipid solubility of the individual PFC. Accordingly, other investigators also found cellular PFC effects that correlated with the agent's lipophilicity but were independent of density and vapor pressure otherwise (23,39). Perfluorohexane has relatively poor lipid solubility, about four times less than that of perfluorooctylbromide.…”

Section: Discussionmentioning

confidence: 97%

Perfluorocarbon attenuates response of concanavalin A-stimulated mononuclear blood cells without altering ligand-receptor interaction

Haufe¹,

Luther²,

Kotzsch³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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(PFC) in acute lung injury is associated with anti-inflammatory effects. A direct impact on leukocytic function may be involved. To further elucidate PFC effects on cellular activation, we compared in an in vitro model the response of concanavalin A (ConA)-stimulated lymphocytes and monocytes exposed to perfluorohexane. We hypothesized that perfluorohexane attenuates the action of the lectin ConA by altering stimulant-receptor interaction on the cell surface. Mononuclear blood cells were stimulated by incubation with ConA in the presence of different amounts of perfluorohexane. The response of lymphocytes and monocytes was determined by means of IL-2 secretion and tissue factor (TF) expression, respectively. The influence of perfluorohexane on cell-surface binding of fluorescence-labeled ConA was studied using flow cytofluorometry and fluorescence microscopy. Perfluorohexane itself did not induce a cellular activation but significantly inhibited both monocytic TF expression and, to a far greater extent, IL-2 secretion of ConAstimulated mononuclear blood cells. The effect of perfluorohexane was due neither to an alteration of cell viability nor to a binding of the stimulant. The amount of cell surface-bound ConA was not altered by perfluorohexane, and the overall pattern of ConA receptor rearrangement did not differ between controls and treated cells. In the present study, we provide further evidence for an anti-inflammatory effect of PFC that might be beneficial in states of pulmonary hyperinflammation. A PFC-induced alteration of stimulant-receptor interaction on the surface membrane does not seem to be the cause of attenuated cell activation.acute lung injury; anti-inflammatory; immune cells; cell-surface receptor IN NUMEROUS STUDIES of experimental and human acute lung injury, beneficial effects of liquid ventilation with perfluorocarbons (PFC) have been demonstrated (16,17,21,22). Application of the biochemically inert liquids resulted in improved gas exchange, lung mechanics, and ventilation/perfusion matching. In part, these observations may be due to several unique properties of PFC such as their high density, an impressive oxygen-carrying capacity, and low surface tension. Besides a positive influence on pulmonary function, animals treated with liquid ventilation also exhibited histological evidence of attenuated lung injury and concomitantly reduced leucocytic infiltration (7,17,27,28). Whereas some authors (3, 14, 35) attributed this reduced pulmonary inflammation exclusively to mechanical phenomena (e.g., lavage of alveolar fluid, water-insoluble PFC forming a barrier between lung epithelium and inflammatory cells and mediators), PFC may also directly influence immune cell function. In support of the latter suggestion, our group as well as other investigators found a compromised responsiveness of phagocytic cell populations in terms of cytokine secretion, chemotaxis, adherence, and release of reactive oxygen species in vitro (4,19,26,32,34). Previous in vivo studies using liquid and aerosolized PFC ...

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Section: Discussionmentioning

confidence: 97%

Perfluorocarbon attenuates response of concanavalin A-stimulated mononuclear blood cells without altering ligand-receptor interaction

Haufe¹,

Luther²,

Kotzsch³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…However, recent trials did not show any clinical benefit for patients treated with PLV when compared with CMV. Some studies have focused on antiinflammatory effects of PLV (2,7,9,(25)(26)(27). Because suppression of the inflammatory response might interfere with lung defense in case of bacterial pneumonia, possible interactions between bacteria and fluorocarbons need to be investigated systematically before recommendations can be given for clinical use of PLV.…”

Section: Discussionmentioning

confidence: 99%

Influence of Partial Liquid Ventilation on Bacterial Growth and Alveolar Expansion in Newborn Rabbits with Group B-Streptococcal Pneumonia

et al. 2003

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“…In recent years, the major studies regarding liquid ventilation have focused on animal experiments or in vitro experiments with few clinical trials. Based on these animal studies and cell experiments, liquid ventilation holds promise to improve low pulmonary compliance and gas exchange in addition to reducing pulmonary inflammatory responses, and ultimately improving the prognosis of animals with ARDS (6)(7)(8)(9)(10)(11)(12)(13)(14). However, the results of clinical randomized controlled trials (RCTs) and basic research have produced conflicting results, and the outlook of liquid ventilation has been disappointing.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of patients require endotracheal intubation and positive pressure ventilation (1,2) and account for millions of days spent in intensive care units (5). In recent years, treatments of ALI/ARDS with improved efficacy have been sought, and studies have indicated that liquid ventilation with perfluorocarbon (PFC) compounds is a promising therapeutic approach (6)(7)(8)(9)(10)(11)(12)(13)(14). PFC is of interest for the treatment of ALI/ARDS due to the unique physicochemical properties, such as high solubility for oxygen, and the anti-inflammatory effects.…”

Section: Introductionmentioning

confidence: 99%

“…Liquid ventilation or aerosolized PFC has been demonstrated to improve gas exchange and improve pulmonary compliance compared with conventional mechanical ventilation in a variety of animal models of ALI/ARDS (6)(7)(8). Specifically, PFC has been shown to reduce levels of cytokines, chemokines and other mediators of pulmonary inflammation in both in vivo and in vitro models (9)(10)(11)(12)(13)(14). However, the understanding of the underlying mechanisms remains poor, in particular of the mechanisms associated with the PFC-induced anti-inflammatory effects.…”

Section: Introductionmentioning

confidence: 99%

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The effects of perfluorocarbon on ICAM-1 expression in LPS-induced A549 cells and the potential mechanism

Cao

Chang

et al. 2016

Mol Med Report

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Abstract. Acute lung injury (ALI)/ARDS is a critical clinical syndrome with high mortality, and the effective therapeutic methods for the treatment remain limited. Previous studies have indicated that liquid ventilation with perfluorocarbon (PFC) may be advantageous over conventional mechanical ventilation in the treatment of ALI/ARDS. Additionally, PFC inhibits the inflammatory response caused by ALI/ARDS. However, the anti-inflammatory mechanism remains to be completely elucidated. In the present study, the aim was to determine the anti-inflammatory mechanism of PFC and the association with microRNA (miR). PFC was used to modulate LPS-induced A549 cells, with the cells divided into four groups: Untreated control group; LPS group, treated with 10 µg/ml LPS; LPS+PFC group, treated with 10 µg/ml LPS and PFC; and PFC group, treated with PFC alone. The intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression levels of each group were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. A549 cells were transfected with miR-17-3p mimics, miR-17-3p inhibitors or negative controls to observe the alterations in the anti-inflammatory effects of PFC. A dual luciferase reporter gene assay was used to determine whether ICAM-1 is a target gene of miR-17-3p. PFC was observed to attenuate the mRNA and protein expression levels of ICAM-1 in LPS-induced A549 cells, with no significant effect on the untreated A549 cells. miR-17-3p was demonstrated to be regulated by PFC. Transfection with miR-17-3p mimics enhanced the anti-inflammatory effects of PFC, whereas the miR-17-3p inhibitor weakened the anti-inflammatory effects of PFC at early time points. To conclude, the current study indicates that ICAM-1 was a target gene of miR-17-3p, and PFC has anti-inflammatory effects. Additionally, the present study is the first report, to the best of our knowledge, that PFC is able to attenuate ICAM-1 expression in LPS-induced A549 cells by increasing miR-17-3p expression.

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Perfluorochemical liquids modulate cell-mediated inflammatory responses

Cited by 29 publications

References 32 publications

Perfluorocarbon attenuates response of concanavalin A-stimulated mononuclear blood cells without altering ligand-receptor interaction

Perfluorocarbon attenuates response of concanavalin A-stimulated mononuclear blood cells without altering ligand-receptor interaction

Influence of Partial Liquid Ventilation on Bacterial Growth and Alveolar Expansion in Newborn Rabbits with Group B-Streptococcal Pneumonia

The effects of perfluorocarbon on ICAM-1 expression in LPS-induced A549 cells and the potential mechanism

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