Apoptosis and Necrosis Induced by Cyclic Mechanical Stretching in Alveolar Type II Cells

Hammerschmidt, Stefan; Kühn, Hartmut; Grasenack, Thomas; Geßner, Christian; Wirtz, Hubert

doi:10.1165/rcmb.2003-0136oc

Cited by 105 publications

(92 citation statements)

References 33 publications

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“…Similar studies in ATII cells have Stretch-induced gene transfer and the cytoskeleton RC Geiger et al had similar findings, and have also shown that these levels of stretch do not induce necrosis. 16 Taken together, these results suggest that cell proliferation is not required for stretch-increased transfection efficiency.…”

Section: Cyclic Stretch Causes Increased Gene Expression Without Incrmentioning

confidence: 80%

Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

et al. 2006

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Cyclic stretch is known to alter a number of cellular and subcellular processes, including those involved in nonviral gene delivery. We have previously shown that moderate equibiaxial cyclic stretch (10% change in basement membrane area, 0.5 Hz, 50% duty cycle) of human pulmonary A549 cells enhances gene transfer and expression of reporter plasmid DNA in vitro, and that this phenomena may be due to alterations in cytoplasmic trafficking. Although the path by which plasmid DNA travels through the cytoplasm toward the nucleus is not well understood, the cytoskeleton and the constituents of the cytoplasm are known to significantly hinder macromolecular diffusion. Using biochemical techniques and immunofluorescence microscopy, we show that both the microfilament and microtubule networks are significantly reorganized by equibiaxial cyclic stretch. Prevention of this reorganization through the use of cytoskeletal stabilizing compounds mitigates the stretchinduced increase in gene expression, however, depolymerization in the absence of stretch is not sufficient to increase gene expression. These results suggest that cytoskeletal reorganization plays an important role in stretch-induced gene transfer and expression. Gene Therapy (2006) 13, 725-731.

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Section: Cyclic Stretch Causes Increased Gene Expression Without Incrmentioning

confidence: 80%

Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

et al. 2006

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“…The biological responses of epithelial cells to deformation are numerous: for example, cyclic deformation of rat primary alveolar epithelial cells increases the level of cell death compared with static deformation (56); cyclic stretch induces apoptosis and necrosis in alveolar type II cells (25); stretch increases paracellular permeability by disrupting tight-junction structure and function (6); and deformation induces inflammatory signaling (59). Mechanical events such as stress failure of the plasma membrane (11,58) underlie potential mechanisms of damage in ventilator-induced lung injury (57).…”

Section: Discussionmentioning

confidence: 99%

Transient elastohydrodynamic drag on a particle moving near a deformable wall

Weekley

Waters

Jensen

2006

The Quarterly Journal of Mechanics and Applied Mathematics

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Naire, Shailesh, and Oliver E. Jensen. Epithelial cell deformation during surfactant-mediated airway reopening: a theoretical model. J Appl Physiol 99: 458 -471, 2005. First published March 31, 2005 doi:10.1152/japplphysiol.00796.2004.-A theoretical model is presented describing the reopening by an advancing air bubble of an initially liquid-filled collapsed airway lined with deformable epithelial cells. The model integrates descriptions of flow-structure interaction (accounting for nonlinear deformation of the airway wall and viscous resistance of the airway liquid flow), surfactant transport around the bubble tip (incorporating physicochemical parameters appropriate for Infasurf), and cell deformation (due to stretching of the airway wall and airway liquid flows). It is shown how the pressure required to drive a bubble into a flooded airway, peeling apart the wet airway walls, can be reduced substantially by surfactant, although the effectiveness of Infasurf is limited by slow adsorption at high concentrations. The model demonstrates how the addition of surfactant can lead to the spontaneous reopening of a collapsed airway, depending on the degree of initial airway collapse. The effective elastic modulus of the epithelial layer is shown to be a key determinant of the relative magnitude of strains generated by flow-induced shear stresses and by airway wall stretch. The model also shows how epithelial-layer compressibility can mediate strains arising from flow-induced normal stresses and stress gradients. recruitment; atelectrauma; volutrauma; fluid-structure interaction; surface tension SUCCESSFUL RECRUITMENT OF liquid-filled airways is a process of fundamental importance in human respiration, from the first breath onward, and is critical in the treatment of conditions such as infant or acute respiratory distress syndrome (ARDS). It is of particular current interest in the context of ARDS, where atelectrauma [damage to airway epithelium through the repeated opening and closing of airways and alveoli (9, 13, 43)], volutrauma [airway overdistension (56, 58)], and biotrauma (inflammatory airway insult secondary to mechanical injury) are candidate mechanisms of ventilator-induced lung injury (49, 53). Mechanisms of atelectrauma, for example, involve processes interacting over widely varying length scales: at the scale of the whole lung (involving forced inflation of a heterogeneous airway network); at the scale of an individual airway (where surface tension, airway compliance, and airway liquid viscosity are significant); at the scale of an airway epithelial cell (deforming in response to its local mechanical environment); and at the scale of individual molecules (for example epithelial-cell mechanosensors such as stretchactivated ion channels). Mathematical and computational models provide powerful tools with which to integrate descriptions of processes operating across such disparate scales. This paper seeks to contribute to the development of a theoretical framework for airway recruitment and specifically aims ...

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“…1,2 The primarily biological mechanisms include the release of inflammatory mediators and oxygen radicals, leading to end-organ epithelial cell apoptosis and organ dysfunction. [3][4][5] In a previous study, a high tidal volume in mouse lung could induce the activation of c-Jun N-terminal kinase (JNK), an increase in macrophage inflammatory protein-2 (MIP-2) expression, and the migration of neutrophil into the lung. 6 Activated JNK is dependent on the activation of apoptosis signal-related kinase 1 (ASK1), which is identified as a member of the mitogen-activated protein kinase (MAPK) family, in cultured bronchial epithelium.…”

Section: Introductionmentioning

confidence: 99%

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury

Yang

Song

Wang

et al. 2013

Laboratory Investigation

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Hypercapnic acidosis may attenuate ventilator-induced lung oxidative stress injury and alveolar cell apoptosis, but the underlying mechanisms are poorly understood. We examined the effects of hypercapnic acidosis on the role of apoptosis signal-regulating kinase 1 (ASK1), which activates the c-Jun N-terminal kinase (JNK) and p38 cascade in both apoptosis and oxidative reactions, in high-pressure ventilation stimulated rat lungs. Rats were ventilated with a peak inspiratory pressure (PIP) of 30 cmH 2 O for 4 h and randomly given FiCO 2 to achieve normocapnia (PaCO 2 at 35-45 mm Hg) or hypercapnia (PaCO 2 at 80-100 mm Hg); normally ventilated rats with PIP of 15 cmH 2 O were used as controls. Lung injury was quantified by gas exchange, microvascular leaks, histology, levels of inflammatory cytokines, and pulmonary oxidative reactions. Apoptosis through the ASK1-JNK/p38 mitogen-activated protein kinase (MAPK) cascade in type II alveolar epithelial cells (AECIIs) were evaluated by examination of caspase-3 activation. The results showed that injurious ventilation caused significant lung injury, including deteriorative oxygenation, changes of histology, and the release of inflammatory cytokines. In addition, the high-pressure mechanical stretch also induced apoptosis and caspase-3 activation in the AECIIs. Hypercapnia attenuated these responses, suppressing the ASK1 signal pathways with its downstream kinase phosphorylation of p38 MAPK and JNK, and caspase-3 activation. Thus, hypercapnia can attenuate cell apoptosis and oxidative stress damage in rat lungs during injurious ventilation, at least in part, due to the suppression of the ASK1-JNK/p38 MAPK pathways.

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Apoptosis and Necrosis Induced by Cyclic Mechanical Stretching in Alveolar Type II Cells

Cited by 105 publications

References 33 publications

Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

Transient elastohydrodynamic drag on a particle moving near a deformable wall

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury

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