Acid exposure disrupts mucus secretion and impairs mucociliary transport in neonatal piglet airways

Liao, Yan Shin J.; Kuan, Shin Ping; Guevara, Maria Valentina; Collins, E. N.; Atanasova, Kalina R.; Dadural, Joshua S.; Vogt, Kevin; Schurmann, Veronica; Bravo, Laura; Eken, Eda; Sponchiado, Mariana; Reznikov, Leah R.

doi:10.1152/ajplung.00025.2020

Cited by 7 publications

(44 citation statements)

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“…Bethanechol chloride (Selleckchem) was dissolved in 0.9% saline to final concentration of 8 mg/ml and sterilized with a 0.22 µm filter (Millex GP) [16]. Acetyl-beta-methacholine-chloride (Sigma) was dissolved in 0.9% saline for ex vivo application [18]. Drugs used in the Ussing chamber studies: amiloride hydrochloride hydrate (Sigma); carbamylcholine chloride (carbachol; Sigma); forskolin (Sigma); 3-isobutyl-1-methylxanthine (Sigma); Glyh-101 (a gift from the…”

Section: Chemicals and Drugsmentioning

confidence: 99%

“…Following euthanasia, the caudal left lung of each piglet was excised and the main bronchus cannulated; three sequential 5 ml lavages of 0.9% sterile saline were administered as previously described [16,18,20]. The recovered material was pooled, spun at 500 X g, and supernatant stored at -80°C.…”

Section: Bronchoalveolar Lavage and Elisamentioning

confidence: 99%

“…The recovered material was pooled, spun at 500 X g, and supernatant stored at -80°C. A porcine MUC5AC (LSBio, LS-F45847-1) and porcine MUC5B (LSBio, LS-F45852-1) ELISA was performed according to the manufacturer's instructions in duplicate as previously described [18]. The ELISA was read using a filter-based accuSkan FC micro photometer (Fisher Scientific).…”

Section: Bronchoalveolar Lavage and Elisamentioning

confidence: 99%

“…Tissues were sectioned at a thickness of 10μm and mounted onto SuperFrost Plus microscope slides (ThermoFisher Scientific). We used immunofluorescence procedures and analyses similar to those previously described [18,20,21]. We used the following anti-mucin antibodies: rabbit anti-MUC5B (1:500; Santa Cruz, Cat.…”

Section: Immunofluorescence In Tracheal Cross Sectionsmentioning

confidence: 99%

“…We measured mucus secretion using previously described methods [18,22]. Briefly, 3-4 rings of trachea were removed post-mortem and the outside of the tracheas were wrapped in gauze soaked with 5 ml of the following: 135 mM NaCl, 2.4 mM K2HPO4, 0.6 mM KH2PO4, 1.2 mM CaCl2, 1.2 mM MgCl2, 10 mM dextrose, 5 mM HEPES, pH 7.4 (NaOH), 1.5 mg/ml of methacholine, and 100 μM bumetanide [18]. Tracheas were then placed in a 37 ºC temperature-controlled humidified incubator for 3 hours.…”

Section: Mucus Secretion Assay Ex Vivomentioning

confidence: 99%

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Durable Changes to Airway Mucus and Fluid Secretion Following Cholinergic Challenge

Liao

Collins

Guevara

et al. 2020

Preprint

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Number of Tables: 1Conflict of interest statement: None declared. AbstractPurpose: Mucus abnormalities are central to the pathophysiology of several chronic airway diseases. Mucus secretion and clearance are regulated, in part, by cholinergic innervation.Prolonged cholinergic stimulation may contribute to mucus abnormalities in disease. Thus, we tested the hypothesis that prolonged cholinergic stimulation gives rise to lasting mucus abnormalities in airways. Methods:We delivered aerosolized bethanechol, a cholinergic agonist, to pig airways. Fortyeight hours later, we measured mucus secretion and mucociliary transport in tracheal segments ex vivo. Tracheal and bronchoalveolar lavage concentrations of the major secreted mucus glycoproteins, mucin5B (MUC5B) or mucin5AC (MUC5AC), were measured with ELISA and antibody labeling. Pig airway epithelia were cultured at the air-liquid interface and treated with bethanechol for forty-eight hours. Stimulated fluid secretion was measured with reflected microscopy and Ussing chambers were used to measure ion transport.Results: Airways from bethanechol-challenged pigs exhibited sheet-like mucus films, which were not associated with a greater abundance of MUC5AC or MUC5B. Epithelia treated with bethanechol had diminished fluid secretion and decreased Cltransport. However, mucus and fluid alterations were not associated with impaired mucociliary transport. Conclusions:These data suggest that cholinergic transmission induces sustained alterations in airway mucus properties. Such defects might compound and/or contribute to persistent mucus phenotypes found after the resolution of airway inflammation.

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Section: Chemicals and Drugsmentioning

confidence: 99%

Section: Bronchoalveolar Lavage and Elisamentioning

confidence: 99%

Section: Bronchoalveolar Lavage and Elisamentioning

confidence: 99%

Section: Immunofluorescence In Tracheal Cross Sectionsmentioning

confidence: 99%

Section: Mucus Secretion Assay Ex Vivomentioning

confidence: 99%

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Durable Changes to Airway Mucus and Fluid Secretion Following Cholinergic Challenge

Liao

Collins

Guevara

et al. 2020

Preprint

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Glutathione and bicarbonate nanoparticles improve mucociliary transport in cystic fibrosis epithelia

Cho,

Rivers,

Lim

et al. 2023

Int Forum Allergy Rhinol

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IntroductionCystic fibrosis (CF) airway disease is characterized by thick mucus and impaired mucociliary transport (MCT). Loss of functional cystic fibrosis transmembrane receptor (CFTR) leads to acidification and oxidation of airway surface mucus. Replacing bicarbonate (HCO3−) topically fails due to rapid reabsorption and neutralization, while the scavenging antioxidant, glutathione sulfhydryl (GSH), is also rapidly degraded. The objective of this study is to investigate GSH/NaHCO3 nanoparticles as novel strategy for CF airway disease.MethodsGSH/NaHCO3 poly (lactic‐co‐glycolic acid) nanoparticles were tested on primary CF (F508del/F508del) epithelial cultures to evaluate dose‐release curves, surface pH, toxicity, and MCT indices using micro‐optical coherence tomography. In vivo tests were performed in three rabbits to assess safety and toxicity. After 1 week of daily injections, histopathology, computed tomography (CT), and blood chemistries were performed and compared to three controls. Fluorescent nanoparticles were injected into a rabbit with maxillary sinusitis and explants visualized with confocal microscopy.ResultsSustained release of GSH and HCO3− with no cellular toxicity was observed over 2 weeks. Apical surface pH gradually increased from 6.54 ± 0.13 (baseline) to 7.07 ± 0.10 (24 h) (p < 0.001) and 6.87 ± 0.05 at 14 days (p < 0.001). MCT, ciliary beat frequency, and periciliary liquid were significantly increased. When injected into the maxillary sinuses of rabbits, there were no changes to histology, CT, or blood chemistries. Nanoparticles penetrated rabbit sinusitis mucus on confocal microscopy.ConclusionFindings suggest that GSH/NaHCO3− nanoparticles are a promising treatment option for viscous mucus in CF and other respiratory diseases of mucus obstruction such as chronic rhinosinusitis.

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Activation of ASIC3/ERK pathway by paeoniflorin improves intestinal fluid metabolism and visceral sensitivity in slow transit constipated rats

Deng,

Zhao,

Zhou

et al. 2024

The Kaohsiung J of Med Scie

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Slow transit constipation (STC) is one of the most common gastrointestinal disorders in children and adults worldwide. Paeoniflorin (PF), a monoterpene glycoside compound extracted from the dried root of Paeonia lactiflora, has been found to alleviate STC, but the mechanisms of its effect remain unclear. The present study aimed to investigate the effects and mechanisms of PF on intestinal fluid metabolism and visceral sensitization in rats with compound diphenoxylate‐induced STC. Based on the evaluation of the laxative effect, the abdominal withdrawal reflex test, enzyme‐linked immunosorbent assay, quantitative real‐time polymerase chain reaction, western blot, and immunohistochemistry were used to detect the visceral sensitivity, fluid metabolism‐related proteins, and acid‐sensitive ion channel 3/extracellular signal‐regulated kinase (ASIC3/ERK) pathway‐related molecules. PF treatment not only attenuated compound diphenoxylate‐induced constipation symptoms and colonic pathological damage in rats but also ameliorated colonic fluid metabolic disorders and visceral sensitization abnormalities, as manifested by increased colonic goblet cell counts and mucin2 protein expression, decreased aquaporin3 protein expression, improved abdominal withdrawal reflex scores, reduced visceral pain threshold, upregulated serum 5‐hydroxytryptamine, and downregulated vasoactive intestinal peptide levels. Furthermore, PF activated the colonic ASIC3/ERK pathway in STC rats, and ASIC3 inhibition partially counteracted PF's modulatory effects on intestinal fluid and visceral sensation. In conclusion, PF alleviated impaired intestinal fluid metabolism and abnormal visceral sensitization in STC rats and thus relieved their symptoms through activation of the ASIC3/ERK pathway.

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Acid exposure disrupts mucus secretion and impairs mucociliary transport in neonatal piglet airways

Cited by 7 publications

References 58 publications

Durable Changes to Airway Mucus and Fluid Secretion Following Cholinergic Challenge

Durable Changes to Airway Mucus and Fluid Secretion Following Cholinergic Challenge

Glutathione and bicarbonate nanoparticles improve mucociliary transport in cystic fibrosis epithelia

Activation of ASIC3/ERK pathway by paeoniflorin improves intestinal fluid metabolism and visceral sensitivity in slow transit constipated rats

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