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

Haufe, Dirk; Luther, Thomas; Kotzsch, Matthias; Knels, Lilla; Koch, Thea

doi:10.1152/ajplung.00432.2003

Cited by 11 publications

(11 citation statements)

References 41 publications

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“…There are no animal trials using PFH in the setting of bacterial lung infection, and the experimental protocols of all studies performed in this field were too short to allow development of VAP (3,8,13,45). However, our in vitro results support the assumption that despite previously demonstrated anti-inflammatory effects (15,25), PFH does not seem to impair lung bactericidal defense, and therefore our initial hypothesis cannot be confirmed.…”

Section: Discussioncontrasting

confidence: 55%

“…In this context, vaporized PFH was associated with improved oxygenation and lung mechanics in experimental ARDS, protected animals from ventilator-induced lung injury, and improved lung histology in oleic acid-injured pigs to a far greater degree compared with liquid ventilation (3,8,13,45). Whether the anti-inflammatory effects of PFH shown by us in recent in vitro studies contribute to this organoprotection remains unclear (15,25).…”

Section: Discussionmentioning

confidence: 93%

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Leukocyte antibacterial functions are not impaired by perfluorocarbon exposure in vitro

Haufe¹,

Koenigshausen²,

Knels³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Application of liquid, aerosolized, and vaporized perfluorocarbons (PFC) in acute lung injury has shown anti-inflammatory effects. Although this may be beneficial in states of pulmonary hyperinflammation, it also could increase susceptibility to nosocomial lung infection. We hypothesized that PFC impair cellular host defense and therefore investigated in an in vitro model the influence of perfluorohexane (PFH) on crucial mechanisms of bacterial elimination in human neutrophils and monocytes. Using scanning and transmission electron microscopy, we could show membrane-bound and ingested PFH particles that morphologically did not alter adherence and phagocytosis of Escherichia coli or leukocyte viability. The amount of adherent and phagocytosed bacteria as determined by flow cytometry was not influenced in cells only pretreated with PFH for 1 and 4 h. When PFH was present during E. coli challenge, bacterial adherence was decreased in polymorphonuclear neutrophils, but respective intracellular uptake was not impaired and was even significantly promoted in monocytes. Overall, E. coli-induced respiratory burst capacity was not reduced by PFH. Our findings provide evidence that key functions of innate host defense are not compromised by PFH treatment in vitro.phagocytosis; burst; perfluorohexane; anti-inflammatory; immune LIQUID VENTILATION WITH PERFLUOROCARBONS (PFC) has been successfully applied in experimental and human acute lung injury (18,20,27,36). Beside positive effects on gas exchange, lung mechanics, and ventilation/perfusion matching, animals treated with liquid ventilation also exhibited attenuated pulmonary damage with concomitant reduction in pulmonary neutrophil sequestration (19,21,32,39). A clinical trial investigating PFC treatment in trauma patients with acute lung injury demonstrated reduced neutrophil counts and decreased levels of proinflammatory cytokines in bronchoalveolar lavage fluid (7). Although removal of alveolar inflammatory exudate by dense, water-insoluble PFC probably contributes to mitigation of pulmonary hyperinflammation, a direct interference with immune cell function may also be involved. This proposition is supported by recent in vivo studies using aerosolized PFC in a surfactant-washout model that reported PFC to decrease mRNA expression of proinflammatory cytokines and adhesion molecules in lung tissue samples as well as in microdissected alveolar macrophages and pulmonary parenchymal cells (42,49,50). Further evidence for cellular anti-inflammatory effects of PFC is provided by in vitro experiments showing a decreased response of activated polymorphonuclear neutrophils (PMN) and monocytic cells in terms of cytokine secretion, chemotaxis, cyclooxygenase-2 (COX-2) expression, and NF-B activation (5,25,37,46,51). Liquid ventilation with PFC did not result in improved survival or reduced need for ventilatory support in recent multicenter trials of patients with acute respiratory distress syndrome (ARDS) (17, 24). Nevertheless, intrinsic anti-inflammatory properties of PFC might b...

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 93%

Leukocyte antibacterial functions are not impaired by perfluorocarbon exposure in vitro

Haufe¹,

Koenigshausen²,

Knels³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Evidence for this barrier effect is supported by other studies [21,22]. Another mechanism implicated in the biological effects of PFC is related to the fact that PFC is able to partition into the lipid component of cellular membranes and the cytoplasm [23], where PFC can execute its nonspecific cell membrane stabilization by interfering with (1) the interaction between stimulant and receptor, (2) the transmembrane signal transduction, and (3) the transduction of intracellular signaling pathways [23][24][25]. So it can be assumed that PFC directly alters the cellular surface membrane, thereby reducing the intracellular signaling cascade and the subsequent inflammatory response.…”

Section: Discussionmentioning

confidence: 81%

Cytoprotection of Perfluorocarbon on PMVECs In Vitro

Wang

Wei

et al. 2012

Inflammation

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Lipopolysaccharide (LPS) can activate endothelial cells and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in the activation of nuclear factor (NF)-κB. A number of studies have demonstrated the cytoprotective action of perfluorocarbon (PFC) both in vivo and in vitro, but the exact mechanisms have yet to be elucidated. In this study, we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated pulmonary vascular endothelial cells (PMVECs). Intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8) were significantly increased in the LPS-stimulated PMVECs groups. The expression of TLR-4 mRNA and protein in LPS groups was markedly increased. Meanwhile, NF-κB was activated. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-α, and IL-8; the expression of TLR-4 mRNA; and the activity of NF-κB. LPS can induce PMVEC inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect PMVECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway.

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“…Initially, a "liquid-PEEP" (21)(22)(23) or a barrier function that prevents ligand receptor contact (24,25) was proposed. But recent data suggest a direct interaction of PFC with intracellular pathways (16,26) or a stabilizing effect on the cellular membrane (27).…”

mentioning

confidence: 99%

Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro

et al. 2006

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Chlamydophila pneumoniae alter the expression of Toll-like receptor (TLR) 4 in alveolar type II (ATII)-cells. Subsequently nuclear factor kappaB (NF-B) is activated and tumor necrosis factor-␣ (TNF-␣) and macrophage inflammatory protein 2 (MIP-2) are produced. Perfluorocarbons (PFC) are beneficial in animals with bacterial pneumonia and reduce production of TNF-␣. Using isolated ATII-cells, it was studied whether PFC prevent C. pneumoniae-induced TNF-␣ and MIP-2 release and what the underlying pathway is. PF5080 preincubation prevented C. pneumoniae-induced secretion of TNF-␣ (43 Ϯ 10 versus 661 Ϯ 41 pg/mL) and MIP-2 (573 Ϯ 41 versus 4786 Ϯ 502 pg/mL). The C. pneumoniae-induced 2.2-fold increase of TNF-␣ Receptor 1 expression was reduced by PF5080. C. pneumoniae reduced cytoplasmatic IB␣ (3.7 Ϯ 0.3 versus 14 Ϯ 1) and increased NF-B p65 (31 Ϯ 7.5 versus 3.6 Ϯ 1.1) compared with control. PF5080 prevented NF-B activation. TLR4 expression was 1.5-fold higher after C. pneumoniae incubation, but remained at control levels after PF5080 pretreatment. After 24 h of C. pneumoniae incubation, in 88 Ϯ 6% of cells bacteria were found in the perinuclear region and in 50% of these cells bacteria adhered to cellular surface. After PF5080 preincubation, C. pneumoniae were in 32 Ϯ 4% attached to and in 5 Ϯ 1% internalized in ATII-cells. Since PF5080 was found in ATII-cell membranes, PF5080 effect could be explained by an alteration of the cellular membrane, preventing activation of the inflammatory cascade. Chlamydophila pneumoniae are obligate intracellular Gram-negative bacteria that cause respiratory infections in pediatric populations and adults (1,2). Recent studies demonstrated the presence of C. pneumoniae in alveolar macrophages and ATII cells in patients with chronic obstructive pulmonary disease (COPD) (3). Whereas most respiratory infections with C. pneumoniae are self-limited (4), bacterial colonization can lead to infectious exacerbations and development of COPD (5). Because detection rate of C. pneumonia varies significantly (6), the clinical relevance of C. pneumoniae is still controversial.The effect of C. pneumoniae on isolated ATII-cells is well characterized. C. pneumoniae inhibit the surfactant metabolism of ATII-cells after internalization (7). Many of C. pneumoniae-induced effects are mediated by cytokines. C. pneumoniae act at the ATII cell membrane to induce the expression of TLR4 (8). TLR signaling is partly mediated by the transcription factor NF-B, which controls the expression of many genes involved in the inflammatory response (9). C. pneumoniae-induced activation of NF-B leads to a release of the chemokine MIP-2 and the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-␣) (8) and its receptor tumor necrosis factor receptor 1 (TNFR1). Together, they play an important role in bacterial infections and modulate the inflammatory process (10).PFC-administered as liquid (11), vapor (12), or gas (13) into the lung-represent an alternative approach to treat respiratory insufficiency. Intrat...

show abstract

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

Cited by 11 publications

References 41 publications

Leukocyte antibacterial functions are not impaired by perfluorocarbon exposure in vitro

Leukocyte antibacterial functions are not impaired by perfluorocarbon exposure in vitro

Cytoprotection of Perfluorocarbon on PMVECs In Vitro

Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro

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