Selected Contribution: Airway contractility and smooth muscle Ca<sup>2</sup><sup>+</sup>  signaling in lung slices from different mouse strains

Bergner, Albrecht; Sanderson, Michael J.

doi:10.1152/japplphysiol.00272.2003

Cited by 38 publications

(38 citation statements)

References 27 publications

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“…These results indicate that the dynamics of the Ca 2ϩ oscillations (or waves) are a function of the Ca 2ϩ oscillation frequency, and this, in turn, implies that the organization and regulation of the Ca 2ϩ release mechanisms underlying the Ca 2ϩ oscillations is common to both rats and mice. In this case, it seems likely that the different frequencies of Ca 2ϩ oscillations induced by similar concentrations of agonist in rat and mouse SMCs results from a differential activation of the G protein receptors responsible for the production of IP 3 .…”

Section: Discussionmentioning

confidence: 99%

“…For example, mouse airway SMCs seem to have a low Ca 2ϩ sensitivity coupled with fast agonistinduced Ca 2ϩ oscillations, whereas mouse pulmonary arteriole SMCs appear to have higher Ca 2ϩ sensitivity coupled with slow agonist-induced Ca 2ϩ oscillations (1,25,26). Similarly, agonist-induced airway contraction varies between species or different strains of the same species with certain strains of mice and rats displaying spontaneous, innate airway hyperresponsiveness (3,9,17,19,24,35). Understanding how alterations in the regulatory mechanisms that are responsible for this physiological variation between species or strains is extremely valuable because it is possible that similar alterations may also account for enhanced airway contraction in asthma.…”

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confidence: 99%

“…In view of the strainrelated differences in airway responses to agonists (19), we selected a mouse (BALB/c) and rat (Sprague-Dawley) strain with average airway responsiveness for the present study. BALB/c mice display an airway reactivity intermediate between A/J mice and C3H/HeJ, the most and least reactive strains, respectively (3,9). Similarly, Sprague-Dawley rats displayed a midrange response compared with Flinders-sensitive rats and Flinders-resistant rats (23).…”

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confidence: 99%

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The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

Bai

Sanderson²

2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Bai Y, Sanderson MJ. The contribution of Ca 2ϩ signaling and Ca 2ϩ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice. Am J Physiol Lung Cell Mol Physiol 296: L947-L958, 2009. First published April 3, 2009 doi:10.1152/ajplung.90288.2008.-To determine the relative contributions of Ca 2ϩ signaling and Ca 2ϩ sensitivity to the contractility of airway smooth muscle cells (SMCs), we compared the contractile responses of mouse and rat airways with the lung slice technique. Airway contraction was measured by monitoring changes in airway lumen area with phase-contrast microscopy, whereas changes in intracellular calcium concentration ([Ca 2ϩ ]i) of the SMCs were recorded with laser scanning microscopy. In mice and rats, methacholine (MCh) or serotonin induced concentration-dependent airway contraction and Ca 2ϩ oscillations in the SMCs. However, rat airways demonstrated greater contraction compared with mice, in response to agonist-induced Ca 2ϩ oscillations of a similar frequency. Because this indicates that rat airway SMCs have a higher Ca 2ϩ sensitivity compared with mice, we examined Ca 2ϩ sensitivity with Ca 2ϩ -permeabilized airway SMCs in which the [Ca 2ϩ ]i was experimentally controlled. In the absence of agonists, high [Ca 2ϩ ]i induced a sustained contraction in rat airways but only a transient contraction in mouse airways. This sustained contraction of rat airways was relaxed by Y-23672, a Rho kinase inhibitor, but not affected by GF-109203X, a PKC inhibitor. The subsequent exposure of Ca 2ϩ -permeabilized airway SMCs, with high [Ca 2ϩ ]i, to MCh elicited a further contraction of rat airways and initiated a sustained contraction of mouse airways, without changing the [Ca 2ϩ ]i of the SMCs. Collectively, these results indicate that airway SMCs of rats have a substantially higher innate Ca 2ϩ sensitivity than mice and that this strongly influences the transduction of the frequency of Ca 2ϩ oscillations into the contractility of airway SMCs. lung slices; Ca 2ϩ oscillations; confocal microscopy; asthma; hyperresponsiveness ASTHMA IS CHARACTERIZED BY airway inflammation and airway hyperresponsiveness to nonspecific stimulation. Although airway inflammation is known to result in airway remodeling, airway hyperresponsiveness occurs in the early stages of asthma when no obvious airway remodeling is discernable. Consequently, the fundamental mechanism leading to the excessive contraction of airway smooth muscle cells (SMCs) remains unknown. A straightforward hypothesis is that the innate contractility of the SMCs has been enhanced in asthmatic airways. However, the experimental evidence addressing the contractile responses of asthmatic SMCs in vitro is inconsistent. Increased (4, 6, 18, 21), normal (4, 5, 10, 34), and even reduced (12, 33, 37) airway constriction has been reported in human asthmatic or animal airways. These discrepancies may also result from the different protocols, methods, and parameters used to evaluate SMCs contraction.To determine whether the cont...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

Bai

Sanderson²

2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Lungs were filled with 2% low melting agarose (Sigma-Aldrich; catalog A0701), as previously described (30). Live tissues were cut and imaged with a Zeiss Axioskop II fluorescent microscope using Simple PCI software.…”

Section: Microscopy Of Lung Parenchymamentioning

confidence: 99%

Distinct Differentiation Potential of Blood Monocyte Subsets in the Lung

Landsman

Varol

Jung

2007

The Journal of Immunology

274

270

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Peripheral blood monocytes are a population of circulating mononuclear phagocytes that harbor potential to differentiate into macrophages and dendritic cells. As in humans, monocytes in the mouse comprise two phenotypically distinct subsets that are Gr1 high CX 3 CR1 int and Gr1 low CX 3 CR1 high , respectively. The question remains whether these populations contribute differentially to the generation of peripheral mononuclear phagocytes. In this study, we track the fate of adoptively transferred, fractionated monocyte subsets in the lung of recipient mice. We show that under inflammatory and noninflammatory conditions, both monocyte subsets give rise to pulmonary dendritic cells. In contrast, under the conditions studied, only Gr1 low CX 3 CR1 high monocytes, but not Gr1 high CX 3 CR1 int cells, had the potential to differentiate into lung macrophages. However, Gr1 high CX 3 CR1 int monocytes could acquire this potential upon conversion into Gr1 low CX 3 CR1 high cells. Our results therefore indicate an intrinsic dichotomy in the differentiation potential of the two main blood monocyte subsets.

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“…Tie off the trachea and cool the inflated lungs in a bath of PBS at 4°C for 60 minutes. The agarose will gel and stiffen in the airspaces to gently stabilize the lung structure during this interval 5 . Higher agarose concentrations, i.e.…”

Section: Lung Tissue Strip Preparationmentioning

confidence: 99%

Micro-Mechanical Characterization of Lung Tissue Using Atomic Force Microscopy

Liu¹,

Tschumperlin²

2011

JoVE

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Matrix stiffness strongly influences growth, differentiation and function of adherent cells [1][2][3] . On the macro scale the stiffness of tissues and organs within the human body span several orders of magnitude 4 . Much less is known about how stiffness varies spatially within tissues, and what the scope and spatial scale of stiffness changes are in disease processes that result in tissue remodeling. To better understand how changes in matrix stiffness contribute to cellular physiology in health and disease, measurements of tissue stiffness obtained at a spatial scale relevant to resident cells are needed. This is particularly true for the lung, a highly compliant and elastic tissue in which matrix remodeling is a prominent feature in diseases such as asthma, emphysema, hypertension and fibrosis. To characterize the local mechanical environment of lung parenchyma at a spatial scale relevant to resident cells, we have developed methods to directly measure the local elastic properties of fresh murine lung tissue using atomic force microscopy (AFM) microindentation. With appropriate choice of AFM indentor, cantilever, and indentation depth, these methods allow measurements of local tissue shear modulus in parallel with phase contrast and fluorescence imaging of the region of interest. Systematic sampling of tissue strips provides maps of tissue mechanical properties that reveal local spatial variations in shear modulus. Correlations between mechanical properties and underlying anatomical and pathological features illustrate how stiffness varies with matrix deposition in fibrosis. These methods can be extended to other soft tissues and disease processes to reveal how local tissue mechanical properties vary across space and disease progression. Video LinkThe video component of this article can be found at https://www.jove.com/video/2911/ Protocol 1. Lung Tissue Strip Preparation 1. Lung tissue is highly compliant and difficult to cut into strips for AFM characterization. To transiently stabilize the lung structure for cutting, inflate isolated mouse lungs intratracheally with 50 ml/kg body weight of 2% low gel point agarose (prepared in PBS) warmed to 37°C. Tie off the trachea and cool the inflated lungs in a bath of PBS at 4°C for 60 minutes. The agarose will gel and stiffen in the airspaces to gently stabilize the lung structure during this interval 5 . Higher agarose concentrations, i.e. 3-4%, may be used to further enhance tissue stabilization for cutting. 2. Cut the agarose-stabilized mouse lung tissue with a razor or scalpel blade into strips of 5 x 5 mm in length and width and 400 μm in thickness, then wash the strips in a PBS bath pre-warmed to 37°C using a 100 ml glass beaker on a bench-top heated stir plate for 5 minutes to remove residual agarose. To exclude large airways and vessels, cut strips from subpleural regions distant from main stem bronchi. If airways and large vessels are to be imaged, cut strips from lung tissue more proximal to main stem bronchi. AFM Microindentation and Fluorescenc...

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Selected Contribution: Airway contractility and smooth muscle Ca²⁺ signaling in lung slices from different mouse strains

Cited by 38 publications

References 27 publications

The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

Distinct Differentiation Potential of Blood Monocyte Subsets in the Lung

Micro-Mechanical Characterization of Lung Tissue Using Atomic Force Microscopy

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Selected Contribution: Airway contractility and smooth muscle Ca2+ signaling in lung slices from different mouse strains

Cited by 38 publications

References 27 publications

The contribution of Ca2+ signaling and Ca2+ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

The contribution of Ca2+ signaling and Ca2+ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

Distinct Differentiation Potential of Blood Monocyte Subsets in the Lung

Micro-Mechanical Characterization of Lung Tissue Using Atomic Force Microscopy

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Product

Resources

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Selected Contribution: Airway contractility and smooth muscle Ca²⁺ signaling in lung slices from different mouse strains

The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice