American journal of physiology. Lung cellular and molecular physiology
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Am. J. Physiol. Lung Cell Mol. Physiol. · Dec 2010
Inflammation in fetal sheep from intra-amniotic injection of Ureaplasma parvum.
Bronchopulmonary dysplasia is associated with chorioamnionitis and fetal lung inflammation. Ureaplasma species are the bacteria most frequently isolated from chorioamnionitis. Very chronic ureaplasma colonization of amniotic fluid causes low-grade lung inflammation and functional lung maturation in fetal sheep. ⋯ CD3-positive cells in the posterior mediastinal lymph node increased in ureaplasma-exposed animals at 3, 7, and 14 days (P = 0.002). Focal elastin depositions decreased in alveolar septa at 14 days (P = 0.002), whereas α-SMA increased in arteries and bronchioli. U. parvum induced a mild acute inflammatory response and changed elastin and α-SMA deposition in the lung, which may affect lung structure and subsequent development.
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Am. J. Physiol. Lung Cell Mol. Physiol. · Nov 2010
Preexposure to hyperoxia causes increased lung injury and epithelial apoptosis in mice ventilated with high tidal volumes.
Both high tidal volume mechanical ventilation (HV) and hyperoxia (HO) have been implicated in ventilator-induced lung injury. However, patients with acute lung injury are often exposed to HO before the application of mechanical ventilation. The potential priming of the lungs for subsequent injury by exposure to HO has not been extensively studied. ⋯ Caspase-8 activation was observed only in HO-12h+HVHO-4h, indicating the involvement of both pathways. Immunohistochemistry and in vitro stretch studies showed caspase cleavage in alveolar epithelial cells. In conclusion, preexposure to HO followed by HV produced severe lung injury associated with alveolar epithelial cell apoptosis.
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Am. J. Physiol. Lung Cell Mol. Physiol. · Oct 2010
Calcium transient evoked by TRPV1 activators is enhanced by tumor necrosis factor-{alpha} in rat pulmonary sensory neurons.
TNFα, a proinflammatory cytokine known to be involved in the pathogenesis of allergic asthma, has been shown to induce hyperalgesia in somatic tissue via a sensitizing effect on dorsal root ganglion neurons expressing transient receptor potential vanilloid type 1 receptor (TRPV1). Because TRPV1-expressing pulmonary sensory neurons play an important role in regulating airway function, this study was carried out to determine whether TNFα alters the sensitivity of these neurons to chemical activators. Responses of isolated nodose and jugular ganglion neurons innervating the rat lungs were determined by measuring the transient increase in intracellular Ca(2+) concentration ([Ca(2+)](i)). ⋯ A pretreatment with the same concentration of TNFα for a longer duration (∼48 h) did not further increase the response, but pretreatment for a shorter duration (1 h) or with a lower concentration (25 ng/ml, 24 h) failed to enhance the Cap sensitivity. 2) The same TNFα pretreatment also induced similar but less pronounced and less uniform increases in the responses to acid (pH 6.5-5.5), 2-aminoethoxydiphenyl borate (2-APB), a common activator of TRPV1, V2, and V3 channels, and allyl isothiocyanate (AITC), a selective activator of TRPA1 channel. 3) In sharp contrast, the responses to ATP, ACh, and KCl were not affected by TNFα. 4) The TNFα-induced hypersensitivity to Cap was not prevented by pretreatment with indomethacin (30 μM). 5) The immunoreactivity to both TNF receptor types 1 and 2 were detected in rat vagal pulmonary sensory neurons. In conclusion, prolonged treatment with TNFα induces a pronounced potentiating effect on the responses of isolated pulmonary sensory neurons to TRPV1 activators. This action of TNFα may contribute in part to the airway hyperresponsiveness induced by this cytokine.
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Am. J. Physiol. Lung Cell Mol. Physiol. · Oct 2010
The estrogen paradox in pulmonary arterial hypertension.
Idiopathic pulmonary arterial hypertension (PAH) is a disabling condition characterized by PA vasoconstriction and remodeling as well as in situ thrombosis and eventual right heart failure. Idiopathic PAH occurs more frequently in females than in males. The female:male ratio is 1.64 ∼ 3.88:1. ⋯ Here we ask the question: Is estrogen a friend or a foe? According to accumulating evidence, we postulate that the different effects of estrogens on different target cells could account for this paradox, i.e., estrogens may exert beneficial effects only on the increased muscularization of vessel walls, but not on phenotypically altered endothelial cells. The effects of estrogens on the pulmonary vasculature are potent and complex, yet not fully understood. A better mechanistic understanding may allow for future therapeutic interventions in patients with PAH.