Roles of P2X receptors and Ca<sup>2+</sup> sensitization in extracellular adenosine triphosphate‐induced hyperresponsiveness in airway smooth muscle

Oguma, Tetsuya; Ito, Satoru; Kondo, Masashi; Makino, Yasushi; Shimokata, Kaoru; Honjo, Haruo; Kamiya, Kaichiro; Kumakura, Hiroaki

doi:10.1111/j.1365-2222.2007.02719.x

Cited by 44 publications

(33 citation statements)

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“…The differences between that study and ours may be due to the use of mouse and human endothelial cells in the previous study, which also used a long-lasting ATP preparation (ATP␥S). Lung endothelial and epithelial cells have several receptors that could interact with extracellular ATP, including those of the P2Y and P2X families (19,20,27). Particular attention has been paid to the role of P2X 7 in the response to ATP.…”

Section: Discussionmentioning

confidence: 99%

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

McClenahan

Hillenbrand

Kapur

et al. 2009

Clin Vaccine Immunol

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Pneumonia in cattle is an important disease both economically and in terms of animal welfare. Recent evidence in other species has shown ATP to be an important modulator of inflammation in the lung, where it is released by activated alveolar macrophages and damaged lung cells. Whether ATP serves a similar process during infection in the bovine lung is unknown. In the present study, we examined the effects of ATP treatment on the morphology, apoptosis, and permeability of bovine pulmonary epithelial (BPE) cells and bovine pulmonary microvascular endothelial cells (BPMEC). Monolayers of BPE cells underwent striking morphological changes when exposed to ATP that included separation of the cells. Neither BPE cells nor BPMEC exhibited increased apoptosis in response to ATP. BPE cell and BPMEC monolayers displayed virtually identical increases in permeability when exposed to ATP, with a 50% change occurring within the first hour of exposure. Both cell types contained mRNA for the P2X 7 receptor, a known receptor for ATP. In BPE cells, but not BPMEC, the change in permeability in response to ATP was reversed by the addition of a P2X 7 receptor antagonist. If similar permeability changes occur in vivo, they could be a factor in vascular leakage into lung airspaces during pneumonia.Several infectious agents are involved in the bovine respiratory disease complex. Among the bacteria involved in this complex, Mannheimia haemolytica is associated with particularly severe lung inflammation that culminates in extensive lung pathology. One of the hallmark pathological changes associated with M. haemolytica pneumonia is the extensive leakage of vascular products into the lung interstitium and air spaces (24,30). We have previously demonstrated that lipopolysaccharide (LPS) can induce permeability changes in endothelial cells in vitro that would be consistent with vascular leakage. However, the effects are slow, requiring well over 12 h to cause measurable effects on permeability (13). It is possible that the host releases substances in the early pathological response that contribute to the extensive leakage of vascular products into the lung. One such possible substance is ATP.The involvement of extracellular ATP in lung inflammation is a relatively new area of research. Patients with cystic fibrosis, a chronic inflammatory lung disease in humans, have increased levels of ATP in both their sputum and lungs (4). This has been correlated with increased neutrophil numbers in the lung. In a model of asthma, extracellular ATP activated dendritic cells in the lungs, which then stimulated airway inflammation (6). Airway smooth muscle contraction, another physiologic change associated with asthma, is also stimulated by ATP (16). The effects of ATP are not always detrimental. ATP appears to have a protective effect in acute inflammation. Kolosova et al. demonstrated that a long-lasting, nonhydrolyzed form of ATP (ATP␥S) given to mice after transtracheal administration of LPS prevented increases in bronchoalveolar lavage protein and white...

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Section: Discussionmentioning

confidence: 99%

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

McClenahan

Hillenbrand

Kapur

et al. 2009

Clin Vaccine Immunol

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“…ATP modulates airway smooth muscle contractility, exacerbates neurogenic bronchoconstriction via the stimulation of lung afferent nerve terminals, and activates immune cells [2][3][4][5]. Extracellular ATP has been described to play a role in the inflammatory process [6], and the increase in extracellular ATP concentration has been suggested to precipitate exacerbations in COPD [7].…”

Section: Introductionmentioning

confidence: 99%

Adenosine triphosphate in exhaled breath condensate of healthy subjects and patients with chronic obstructive pulmonary disease

et al. 2008

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“…Measurement of adenosine, ATP, and AMP in sputum or exhaled breath condensate has been used as a noninvasive method to track airway inflammation (Huszá r et al, 2002;Esther et al, 2008). Extracellular ATP was reported to sensitize airway smooth muscle cells to contractile agonists (e.g., metacholine) via P2X receptor activation, without enhancing the induced [Ca 2ϩ ] i rise, and the resulting hyper-responsiveness was referred to as "Ca 2ϩ sensitization" (Oguma et al, 2007). Erythromycin therapy has been used to decrease airway secretion in chronic inflammatory airway diseases (Kondo et al, 1998), perhaps by selectively inhibiting Ca 2ϩ influx through P2X receptor channels (Zhao et al, 2000).…”

Section: Diseases Of the Airwaysmentioning

confidence: 99%

Purinergic Signaling in the Airways

Burnstock

Brouns²,

Adriaensen³

et al. 2012

Pharmacol Rev

173

158

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Roles of P2X receptors and Ca²⁺ sensitization in extracellular adenosine triphosphate‐induced hyperresponsiveness in airway smooth muscle

Abstract: Pre-treatment with ATP induces hyperresponsiveness to MCh mediated by Ca2+ sensitization via the P2X receptor in airway smooth muscle. The present findings suggest the possible involvement of both the Rho-kinase and Src pathways in the intracellular mechanism of this phenomenon.

Cited by 44 publications

References 34 publications

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

Adenosine triphosphate in exhaled breath condensate of healthy subjects and patients with chronic obstructive pulmonary disease

Purinergic Signaling in the Airways

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Roles of P2X receptors and Ca2+ sensitization in extracellular adenosine triphosphate‐induced hyperresponsiveness in airway smooth muscle

Abstract: Pre-treatment with ATP induces hyperresponsiveness to MCh mediated by Ca2+ sensitization via the P2X receptor in airway smooth muscle. The present findings suggest the possible involvement of both the Rho-kinase and Src pathways in the intracellular mechanism of this phenomenon.

Cited by 44 publications

References 34 publications

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

Adenosine triphosphate in exhaled breath condensate of healthy subjects and patients with chronic obstructive pulmonary disease

Purinergic Signaling in the Airways

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Roles of P2X receptors and Ca²⁺ sensitization in extracellular adenosine triphosphate‐induced hyperresponsiveness in airway smooth muscle