Perfluorocarbons are taken up by isolated type II pneumocytes and influence its lipid synthesis and secretion

Rüdiger, Mario; Wissel, Heide; Ochs, Matthias; Burkhardt, Wolfram; Proquitté, Hans; Wauer, Roland R.; Stevens, Paul A.; Rüstow, Bernd

doi:10.1097/01.ccm.0000060008.96029.7d

Cited by 8 publications

(17 citation statements)

References 24 publications

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“…These findings appear to be in contrast to two studies suggesting the rapid uptake of fluorescently labeled Rimar 101 and perfluorooctane (i.e., PF5080) by alveolar type II cell membranes and alveolar bodies [58,59]. However, it is unclear if the fluorescent staining of cellular lipid compartments in both studies was indeed due to the uptake of the respective PFC or the result of partitioning of the probe molecule itself from the PFC phase into the lipid compartment.…”

Section: Cellular Uptake Of Pfcs By Passive Diffusioncontrasting

confidence: 78%

Anti-inflammatory effects of perfluorocarbon compounds

Lehmler¹

2008

Expert Review of Respiratory Medicine

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Perfluorocarbon compounds (PFCs) are of interest for the treatment of acute lung injury due to unique physicochemical properties such as high solubility for oxygen. Different respiratory treatment modalities (e.g., liquid ventilation or aerosolized PFCs) have been shown to decrease pulmonary inflammatory responses in addition to improving lung compliance in animal models of lung injury and in clinical trials. Specifically, PFC-based treatment modalities have been shown to reduce levels of cytokines, chemokines and other mediators of pulmonary inflammation in a PFC- and, to some extent, concentration-dependent manner. As a result, neutrophil adhesion, accumulation and activation are reduced in PFC-treated animals and in humans undergoing partial liquid ventilation. Although more fundamental studies of the underlying anti-inflammatory mechanisms are needed, respiratory treatment modalities involving PFCs hold great clinical promise.

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Section: Cellular Uptake Of Pfcs By Passive Diffusioncontrasting

confidence: 78%

Anti-inflammatory effects of perfluorocarbon compounds

Lehmler¹

2008

Expert Review of Respiratory Medicine

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“…A similar effect has been previously described for lamellar bodies (31) and for erythrocytes (27). Therefore, a PFC induced stabilization of cellular membranes (27) is the most likely explanation how PFC prevent the internalization of C. pneumoniae.…”

Section: Discussionsupporting

confidence: 56%

“…To study intracellular PFCdistribution, PF5080 was labeled with 4,4-difluoro-2,6-di-t-butyl-1,3,5,7,8-pentam, ethyl-4bora-3a, 4a-diaza-s-indacene (FEW Chemicals GmbH, Wolfen, Germany) as described (31). Isolated ATII cells were incubated with labeled PF5080 for 20 min and analyzed by confocal microscopy.…”

Section: Methodsmentioning

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...

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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: 83%

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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Perfluorocarbons are taken up by isolated type II pneumocytes and influence its lipid synthesis and secretion

Abstract: Our results suggest that perfluorocarbons are taken up by type II pneumocytes and cause an increased secretion of surfactant, despite a relative reduction in the synthesis of phospholipids.

Cited by 8 publications

References 24 publications

Anti-inflammatory effects of perfluorocarbon compounds

Anti-inflammatory effects of perfluorocarbon compounds

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

Cytoprotection of Perfluorocarbon on PMVECs In Vitro

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