Home
|
Inbox
|
Search
|
View Abstract
A Reducing Agent Impairs Airway Mucociliary Transport In Vivo in Piglets
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A2312 - A Reducing Agent Impairs Airway Mucociliary Transport In Vivo in Piglets
Author Block: M. Pino Argumedo, B. M. Hilkin, N. D. Gansemer, M. J. Welsh, M. Abou Alaiwa; Internal Medicine, University of Iowa, Iowa City, IA, United States.
BACKGROUND:
Mucociliary transport (MCT) of inhaled particles and bacteria plays an important role in respiratory defense. Defective MCT contributes to the pathogenesis of lung disease, such as primary ciliary dyskinesia, cystic fibrosis, chronic bronchitis and asthma. MCT involves mucus and motile cilia; mucus traps particles and pathogens, and cilia propel them out of the lung. The key structural proteins of mucus are mucins, which are highly glycosylated proteins linked by disulfide bonds. Mucins confer mucus with its viscoelastic properties. Reducing agents disrupt disulfide bonds and reduce the viscoelasticity of mucus. To determine the effect of a reducing agent in vivo, we tested the reducing agent, tris(2-carboxyethyl)phosphine (TCEP) on MCT. We studied pigs because they have submucosal glands, anatomy and physiology like humans.
METHODS:
Using a computed tomography (CT) based MCT assay, we examined mucociliary transport in newborn wild-type piglets. Piglets were randomized to receive either intra-tracheal TCEP (10 mM) or intra-tracheal normal saline as a control. Prior to intervention, each piglet received (0.25mg/kg) of methacholine intravenously to induce submucosal gland secretion. Following each intervention, we insufflated 30 tantalum microdisks (300 µm) with a puff of compressed air. The piglets breathed spontaneously to maintain normal airway humidification. Each tantalum microdisk was tracked for a duration of 8 min with a series of CT scans acquired every 9 seconds.
RESULTS:
Intravenous methacholine increased the average velocity and maximum velocity of microdisks that were moving. Methacholine also increased the fraction of microdisks that moved, likely due to stimulation of submucosal gland secretion and an increase in ciliary beat frequency. TCEP did not change the average velocity or maximum velocity of microdisks that were moving. However, TCEP increased the fraction of microdisks that did not move and the fraction of microdisks that had a prolonged delay before beginning to move.
CONCLUSIONS:
These data suggest, that disrupting mucin disulfide bonds with the reducing agent TCEP impaired MCT. Thus, normal mucin structure and viscoelastic properties maybe required for effective MCT.
Author Block: M. Pino Argumedo, B. M. Hilkin, N. D. Gansemer, M. J. Welsh, M. Abou Alaiwa; Internal Medicine, University of Iowa, Iowa City, IA, United States.
BACKGROUND:
Mucociliary transport (MCT) of inhaled particles and bacteria plays an important role in respiratory defense. Defective MCT contributes to the pathogenesis of lung disease, such as primary ciliary dyskinesia, cystic fibrosis, chronic bronchitis and asthma. MCT involves mucus and motile cilia; mucus traps particles and pathogens, and cilia propel them out of the lung. The key structural proteins of mucus are mucins, which are highly glycosylated proteins linked by disulfide bonds. Mucins confer mucus with its viscoelastic properties. Reducing agents disrupt disulfide bonds and reduce the viscoelasticity of mucus. To determine the effect of a reducing agent in vivo, we tested the reducing agent, tris(2-carboxyethyl)phosphine (TCEP) on MCT. We studied pigs because they have submucosal glands, anatomy and physiology like humans.
METHODS:
Using a computed tomography (CT) based MCT assay, we examined mucociliary transport in newborn wild-type piglets. Piglets were randomized to receive either intra-tracheal TCEP (10 mM) or intra-tracheal normal saline as a control. Prior to intervention, each piglet received (0.25mg/kg) of methacholine intravenously to induce submucosal gland secretion. Following each intervention, we insufflated 30 tantalum microdisks (300 µm) with a puff of compressed air. The piglets breathed spontaneously to maintain normal airway humidification. Each tantalum microdisk was tracked for a duration of 8 min with a series of CT scans acquired every 9 seconds.
RESULTS:
Intravenous methacholine increased the average velocity and maximum velocity of microdisks that were moving. Methacholine also increased the fraction of microdisks that moved, likely due to stimulation of submucosal gland secretion and an increase in ciliary beat frequency. TCEP did not change the average velocity or maximum velocity of microdisks that were moving. However, TCEP increased the fraction of microdisks that did not move and the fraction of microdisks that had a prolonged delay before beginning to move.
CONCLUSIONS:
These data suggest, that disrupting mucin disulfide bonds with the reducing agent TCEP impaired MCT. Thus, normal mucin structure and viscoelastic properties maybe required for effective MCT.
|
Home
|
Inbox
|
Search
|