Regulation of secretion from mucous and serous cells in the excised ferret trachea

Kishioka, Chikako; Okamoto, Kosuke; Kim, Jungsoo; Rubin, Bruce K.

doi:10.1016/s0034-5687(01)00214-6

Cited by 40 publications

(24 citation statements)

References 21 publications

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“…Interest in the role of elastase in lung injury was sparked by the observation that unchecked elastase activity, due to a genetic defect in an inhibitor of elastase activity (␣ 1 -antitrypsin deficiency), resulted in an early and sometimes severe form of emphysema (18). Further studies in animal models demonstrated that the intratracheal administration of elastase is associated with goblet cell hyperplasia and increased secretion of mucins and apoptosis of lung epithelial cells (43), supporting a nondegradative role for elastase (34,44). Other studies (38,55) focused on animal models of lung injury demonstrated attenuation of injury with the administration of elastase inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt

Ginzberg

Shannon²,

Suzuki³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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During acute inflammation, neutrophil-mediated injury to epithelium may lead to disruption of epithelial function, including the induction of epithelial apoptosis. Herein, we report the effects of neutrophil transmigration and of purified leukocyte elastase on epithelial cell survival. Neutrophil transmigration induced apoptosis of epithelial cells [control monolayers: 5 ± 1 cells/25 high-power fields (HPF) vs. neutrophil-treated monolayers: 29 ± 10 cells/HPF, P < 0.05, n = 3 as determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay] as did low concentrations (0.1 U/ml) of purified leukocyte elastase (control monolayers: 6.4 ± 2.5% apoptotic vs. elastase: 26.2 ± 2.9% apoptotic, P < 0.05, as determined by cytokeratin 18 cleavage). Treatment with elastase resulted in decreased mitochondrial membrane potential, release of cytochrome c to the cytosol, and cleavage of caspases-9 and -3 as determined by Western blot analysis, implicating altered mitochondrial membrane permeability as a primary mechanism for elastase-induced apoptosis. Additionally, incubation of epithelial cells with leukocyte elastase resulted in an early increase followed by a decrease in the phosphorylation of epithelial Akt, a serine/threonine kinase important in cell survival. Inhibition of epithelial Akt before elastase treatment potentiated epithelial cell apoptosis, suggesting that the initial activation of Akt represents a protective response by the epithelial cells to the proapoptotic effects of leukocyte elastase. Taken together, these observations suggest that epithelial cells exhibit a dual response to cellular stress imposed by leukocyte elastase with a proapoptotic response mediated via early alterations in mitochondrial membrane permeability countered by activation of the survival pathway involving Akt.

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Section: Discussionmentioning

confidence: 99%

Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt

Ginzberg

Shannon²,

Suzuki³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…First, in contrast to mice, the ferret has marked similarities to humans in lung physiology, airway morphology, and cell types [4][5][6][7][8][9]. Second, the expression of CFTR in the ferret airway epithelium and submucosal glands is also identical to that in humans [10,11].…”

Section: Introductionmentioning

confidence: 99%

Developmental Capacity of Ferret Embryos by Nuclear Transfer Using G0/G1-Phase Fetal Fibroblasts1

Li¹,

Sabet²,

Zhou³

et al. 2003

Biology of Reproduction

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With the ultimate goal of establishing experimental protocols necessary for cloning ferrets, the present study has established parameters for the reconstruction of ferret embryos by nuclear transfer (NT) using G0/G1-phase donor fetal fibroblasts. Cumulus-oocyte complexes were harvested from superovulated ferrets and cultured in maturation medium for 24 h. Matured oocytes were then enucleated and injected with the fibroblast nuclei derived from 14-16-h serum-starved cells. Reconstructed embryos were then activated by a combination of electric pulses and chemical stimulations. Subsequently, the reconstructed and activated embryos were either cultured in vitro or transferred to pseudopregnant ferrets to evaluate their developmental capacity in vitro and in vivo. Our results demonstrated that 56.3% of reconstructed embryos (n = 187) cleaved, while 26.0% and 17.6% developed to morula and blastocyst phases in vitro, respectively. The blastocysts derived from NT embryos demonstrated normal morphology by differentially staining as compared to normal blastocysts developed in vivo following fertilization. In vivo developmental studies at 21 days posttransplantation demonstrated 8.8% of reconstructed embryos (n = 91) implanted into the uterine lining of recipients, while 3.3% formed fetuses. However, reconstructed embryos (n = 387) failed to develop to term (42 days). These results demonstrate donor nuclei of G0/G1-phase fetal fibroblast cells can be reprogrammed to support the development of reconstructed ferret embryos in vitro and in vivo; however, a significant third-trimester block occurs preventing full-term development.

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“…These blood group antigens can be detected by Dolichos biflorus agglutinin (DBA) lectin. DBA immunohistochemistry has shown specific binding to goblet cells and submucosal glands in ferret trachea (16).…”

Section: Methodsmentioning

confidence: 99%

“…After resting for 1 h, ferret tracheal segments were incubated for 30 min with KHS to measure constitutive MG secretion (period 1) and then incubated for 30 min in KHS with a secretagogue or KHS alone to measure stimulated MG secretion (period 2). To evaluate MG secretion in response to cholinergic or serine protease stimulation, methacholine (MCh) at 10 Ϫ7 M or human neutrophil elastase (HNE; Elastin Products, Owensville, MO) at 10 Ϫ8 M was used based on our previous studies (16).…”

Section: Methodsmentioning

confidence: 99%

Secretory phospholipases A₂stimulate mucus secretion, induce airway inflammation, and produce secretory hyperresponsiveness to neutrophil elastase in ferret trachea

Okamoto¹,

Kim²,

Rubin³

2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Secretory phospholipases A(2) (sPLA(2)) are increased in the bronchoalveolar lavage fluid of patients with asthma and acute respiratory distress syndrome. Intratracheal sPLA(2) instillation induces acute lung injury in the rat and guinea pig. We hypothesized that sPLA(2) would stimulate mucus secretion in vitro and that intratracheal sPLA(2) exposure would induce mucus hypersecretion and airway inflammation in the ferret trachea in vivo. In vitro, porcine pancreatic sPLA(2) at a concentration of 0.5 or 5 U/ml significantly increased mucous glycoconjugate (MG) secretion from the excised ferret trachea. P-bromophenacylbromide (a sPLA(2) inhibitor), quercetin (a lipoxygenase inhibitor), or MK-886 (a 5-lipoxygenase inhibitor), each at 10(-4) M, significantly reduced sPLA(2)-induced MG secretion. sPLA(2)-stimulated MG secretion was decreased in Ca(2+)-free medium. In vivo, ferrets were intubated for 30 min once per day for 3 days using an ETT coated with 20 units of porcine pancreatic sPLA(2) mixed in water-soluble jelly. Constitutive MG secretion increased 1 day after sPLA(2) exposure and returned to control 5 days later. Human neutrophil elastase (HNE) at 10(-8) M increased MG secretion in the sPLA(2)-exposed trachea compared with that in the control trachea, but methacholine at 10(-7) M did not. sPLA(2)-induced secretory hyperresponsiveness continued for at least 5 days after sPLA(2) exposure ended. sPLA(2) increased tracheal inflammation, MG secretion, and secretory hyperresponsiveness to HNE probably through enzymatic action rather than by activation of its receptor.

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Regulation of secretion from mucous and serous cells in the excised ferret trachea

Cited by 40 publications

References 21 publications

Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt

Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt

Developmental Capacity of Ferret Embryos by Nuclear Transfer Using G0/G1-Phase Fetal Fibroblasts1

Secretory phospholipases A₂stimulate mucus secretion, induce airway inflammation, and produce secretory hyperresponsiveness to neutrophil elastase in ferret trachea

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Regulation of secretion from mucous and serous cells in the excised ferret trachea

Cited by 40 publications

References 21 publications

Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt

Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt

Developmental Capacity of Ferret Embryos by Nuclear Transfer Using G0/G1-Phase Fetal Fibroblasts1

Secretory phospholipases A2stimulate mucus secretion, induce airway inflammation, and produce secretory hyperresponsiveness to neutrophil elastase in ferret trachea

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Secretory phospholipases A₂stimulate mucus secretion, induce airway inflammation, and produce secretory hyperresponsiveness to neutrophil elastase in ferret trachea