Interfacial sensing by alveolar type II cells: a new concept in lung physiology?

Ravasio, Andrea; Hobi, Nina; Bertocchi, Cristina; Jesacher, Alexander; Dietl, Paul; Haller, Thomas

doi:10.1152/ajpcell.00427.2010

Cited by 28 publications

(42 citation statements)

References 54 publications

(63 reference statements)

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“…Furthermore, since cell flattening occurred considerably earlier than cell damage, we conclude that, at least at the beginning, it is not a harmful event (56). Importantly, these data directly show that the I AL exerts a mechanical deforming stress on the cells, which is in accordance with what has been postulated and shown by different methods in recent studies before (55,56).…”

Section: Methodssupporting

confidence: 89%

“…Since bending of the I AL started at about the same time as cell flattening, this suggests that the surface tension of the I AL is in a comparable range as the reported elastic modulus of AT II cells (3). Furthermore, since cell flattening occurred considerably earlier than cell damage, we conclude that, at least at the beginning, it is not a harmful event (56). Importantly, these data directly show that the I AL exerts a mechanical deforming stress on the cells, which is in accordance with what has been postulated and shown by different methods in recent studies before (55,56).…”

Section: Methodssupporting

confidence: 57%

“…Thus the characteristic Ca 2ϩ increase shown in Fig. 1D, which is probably the decisive sensory event in cellinterface contacts (56) and starts as early as ϳ4 min after fluid aspiration (ϭ I AL contact), is unlikely due to osmotic effects. It is also unlikely that this Ca 2ϩ increase is due to plasma membrane damage, as LDH release was detected only after 20 min (see Figs.…”

Section: Conventional Interface Experiments Seementioning

confidence: 91%

“…2) The cellular response is weaker than in conventional interface experiments or may be completely absent (56) 56). Thus this approach is not a mere replication of the conventional interface experiments, and additionally allowed the study of the consequences of a more prolonged interface challenge, which is not possible with the former approach.…”

Section: Conventional Interface Experiments Seementioning

confidence: 99%

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Interfacial stress affects rat alveolar type II cell signaling and gene expression

Hobi

Ravasio

Haller

2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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.) showed that contact of alveolar epithelial type II cells with an air-liquid interface (I AL) leads to a paradoxical situation. It is a potential threat that can cause cell injury, but also a Ca 2ϩ -dependent stimulus for surfactant secretion. Both events can be explained by the impact of interfacial tensile forces on cellular structures. Here, the strength of this mechanical stimulus became also apparent in microarray studies by a rapid and significant change on the transcriptional level. Cells challenged with an IAL in two different ways showed activation/inactivation of cellular pathways involved in stress response and defense, and a detailed Pubmatrix search identified genes associated with several lung diseases and injuries. Altogether, they suggest a close relationship of interfacial stress sensation with current models in alveolar micromechanics. Further similarities between IAL and cell stretch were found with respect to the underlying signaling events. The source of Ca 2ϩ was extracellular, and the transmembrane Ca 2ϩ entry pathway suggests the involvement of a mechanosensitive channel. We conclude that alveolar type II cells, due to their location and morphology, are specific sensors of the IAL, but largely protected from interfacial stress by surfactant release. cell deformation; cell injury; mechanotransduction; microarray; stretch IN THE ALVEOLI, MECHANICAL forces are a constant modulator of tissue geometry and function (4). These forces arise from multiple sources, such as cyclic stretching and compression during respiration, changes in transcapillary pressure, or surface tension at the air-liquid interface (I AL ) (22). They are probably nonuniform in space and time (26,51,67) and impose either physiological responses of the cells, or pathological ones, depending on the type of tissue or the magnitude or abnormality of forces that are at work (reviewed in Refs. 18,66,69,72). In particular, tissue stretch (ϭ tensile strain) has already been shown to be an important determinant of surfactant secretion in alveolar type II (AT II) cells (2,15,36,47,71,73). Studies on single cells revealed that stretch induces an elevation of the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) (23, 73), perhaps via mechanosensitive ion channels like the wellcharacterized transient receptor potential (TRP) vanilloids (reviewed in Refs. 16,77). Recently, the panoply of mechanosensitive mechanisms was expanded by the finding that the I AL , the "normal" microenvironment of the AT II cells (6), may be a strong mechanical incentive as well. Two recent independent studies (55, 56) described a stimulating, but also harmful, effect of an I AL on the AT II cell function. Interestingly, interfacial contact is followed by an increase in [Ca 2ϩ ] i and release of ATP, both of which stimulate secretion (reviewed in Refs. 1, 44, 59). It has even been speculated that this response could act within a feedback loop to continuously monitor and to adjust the physical properties of the interface or the hypophase below.In addition...

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Section: Methodssupporting

confidence: 89%

Section: Methodssupporting

confidence: 57%

Section: Conventional Interface Experiments Seementioning

confidence: 91%

Section: Conventional Interface Experiments Seementioning

confidence: 99%

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Interfacial stress affects rat alveolar type II cell signaling and gene expression

Hobi

Ravasio

Haller

2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…BODIPY-PC incorporates into surfactant (Ravasio et al, 2011). At the beginning of the experiment, cells were stimulated with 100 mM ATP, a potent agonist for LB fusion and surfactant secretion .…”

Section: Actin Coating Of Fused Lbs Is Essential For Surfactant Expulmentioning

confidence: 99%

Actin coating and compression of fused secretory vesicles are essential for surfactant secretion: a role for Rho, formins and myosin II

Miklavc¹,

Hecht²,

Hobi³

et al. 2012

Journal of Cell Science

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130

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SummarySecretion of vesicular contents by exocytosis is a fundamental cellular process. Increasing evidence suggests that post-fusion events play an important role in determining the composition and quantity of the secretory output. In particular, regulation of fusion pore dilation and closure is considered a key regulator of the post-fusion phase. However, depending on the nature of the cargo, additional mechanisms might be essential to facilitate effective release. We have recently described that in alveolar type II (ATII) cells, lamellar bodies (LBs), which are secretory vesicles that store lung surfactant, are coated with actin following fusion with the plasma membrane. Surfactant, a lipoprotein complex, does not readily diffuse out of fused LBs following opening and dilation of the fusion pore. Using fluorescence microscopy, atomic force microscopy and biochemical assays, we present evidence that actin coating and subsequent contraction of the actin coat is essential to facilitate surfactant secretion. Latrunculin B prevents actin coating of fused LBs and inhibits surfactant secretion almost completely. Simultaneous imaging of the vesicle membrane and the actin coat revealed that contraction of the actin coat compresses the vesicle following fusion. This leads to active extrusion of vesicle contents. Initial actin coating of fused vesicles is dependent on activation of Rho and formin-dependent actin nucleation. Actin coat contraction is facilitated by myosin II. In summary, our data suggest that fusion pore opening and dilation itself is not sufficient for release of bulky vesicle cargos and that active extrusion mechanisms are required.

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Bioengineering the Blood‐gas Barrier

Leiby

Raredon

Niklason

2020

Comprehensive Physiology

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Interfacial sensing by alveolar type II cells: a new concept in lung physiology?

Cited by 28 publications

References 54 publications

Interfacial stress affects rat alveolar type II cell signaling and gene expression

Interfacial stress affects rat alveolar type II cell signaling and gene expression

Actin coating and compression of fused secretory vesicles are essential for surfactant secretion: a role for Rho, formins and myosin II

Bioengineering the Blood‐gas Barrier

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