Foetal airway motor tone in prenatal lung development of the pig

Sparrow, Malcolm; Warwick, S.P.; Mitchell, Howard

doi:10.1183/09031936.94.07081416

Cited by 43 publications

(37 citation statements)

References 14 publications

(15 reference statements)

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“…Weichselbaum et al (1996) and Sparrow et al (1999) reported studies on the development of innervation of airway smooth muscle coat in human and porcine lungs using confocal microscopy and various neural markers. These studies demonstrated an extensive neural network enveloping the fetal airways, supporting earlier physiological studies on fetal lungs that reported strong smooth muscle constrictor responses after electrical or agonist stimulation (Sparrow et al 1994). This indicates the presence of functional innervation of the airways in early fetal life.…”

Section: Discussionsupporting

confidence: 74%

Innervation of Pulmonary Neuroendocrine Cells and Neuroepithelial Bodies in Developing Rabbit Lung

Pan

Yeger

Cutz

2004

J Histochem Cytochem.

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S U M M A R YWe investigated the development of innervation of the pulmonary neuroendocrine cell (PNEC) system composed of single cells and organoid cell clusters, neuroepithelial bodies (NEB) in rabbit fetal and neonatal lungs. To visualize the nerve fibers and their contacts with PNECs/NEBs, we used confocal microscopy and multilabel immunohistochemistry (IHC) with pan-neural marker, synaptic vesicle protein 2 (SV2), and serotonin (5-HT) as markers for PNECs/NEBs, and smooth muscle actin or cytokeratin to identify airway landmarks. The numbers and distribution of PNEC/NEB at different stages of lung development (E16, 18, 21, 26, and P2) and the density of innervation were quantified. First PNECs immunoreactive for 5-HT were identified in primitive airway epithelium at E18 as single cells or as small cell clusters with or without early nerve contacts. At E21 a significant increase in the number of PNECs with formation of early innervated NEB corpuscules was observed. The overall numbers of PNECs/NEBs and the density of mucosal, submucosal, and intercorpuscular innervation increased with progressing gestation and peaked postnataly (P2). At term, the majority of NEBs and single PNECs within airway mucosa possessed neural contacts. Such an extensive and complex innervation of the PNEC system indicates a multifunctional role in developing lung and during neonatal adaptation.

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Section: Discussionsupporting

confidence: 74%

Innervation of Pulmonary Neuroendocrine Cells and Neuroepithelial Bodies in Developing Rabbit Lung

Pan

Yeger

Cutz

2004

J Histochem Cytochem.

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“…The airways also contracted strongly to many agonists, e.g., acetylcholine (ACh), histamine, and Substance P, displaying a force per cross-sectional area of smooth muscle and a sensitivity comparable with that of the airways of postnatal animals (9-11). They relax with ␤ -agonists in explants (7) and throughout the airways of the freshly isolated fetal bronchial tree (9,10). The spontaneous activity is unaffected by tetrodoxin, indicating that neural activity is not essential, and by atropine, showing that endogenous ACh is not involved.…”

mentioning

confidence: 90%

“…McCray (7) noted spontaneous activity of epithelial tubules in small fragments of fresh lungs from first-trimester human fetuses and characterized their contractile responses to pharmacologic agents (discussed later). Sparrow and colleagues (9,10) video-recorded sequences of strong spontaneous narrowing of individual airways in the isolated intact bronchial tree in the late first and early second trimesters of fetal pig lung. The spontaneous narrowing moved the lung liquid backward and forward along the airway lumen.…”

mentioning

confidence: 99%

Spontaneous Peristaltic Airway Contractions Propel Lung Liquid through the Bronchial Tree of Intact and Fetal Lung Explants

Schittny

Miserocchi

Sparrow

2000

Am J Respir Cell Mol Biol

140

110

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Spontaneous contractions of the fetal airways are a well recognized but poorly characterized phenomenon. In the present study spontaneous narrowing of the airways was analyzed in freshly isolated lungs from early to late gestation in fetal pigs and rabbits and in cultured fetal mouse lungs. Propagating waves of contraction traveling proximal to distal were observed in fresh lungs throughout gestation which displaced the lung liquid along the lumen. In the pseudoglandular and canalicular stages (fetal pigs) the frequency ranged from 2.3 to 3.3 contractions/min with a 39 to 46% maximum reduction of lumen diameter. In the saccular stage (rabbit) the frequency was 10 to 12/min with a narrowing of ‫ف‬ 30%. In the organ cultures the waves of narrowing started at the trachea in whole lungs, or at the main bronchus in lobes (5.2 Ϯ 1.5 contractions/min, 22 Ϯ 8% reduction of lumen diameter), and as they proceeded distally along the epithelial tubes the luminal liquid was shifted toward the terminal tubules, which expanded the endbuds. Spontaneous narrowing and relaxation of the airways in the developing fetal lung has been described since the early part of the twentieth century. These spontaneous contractions are characteristic of phasic smooth muscle where regular bursts of action potentials give rise to rhythmic mechanical activity, typified by the smooth muscle of the viscera (1). Yet the contraction of mammalian airway smooth muscle in postnatal life is characterized by slow, graded contractions leading to airway narrowing and occurs without the generation of action potentials during membrane depolarization (2, 3). This is classified as tonic smooth muscle, in common with many blood vessels (1). Perhaps the rhythmic contractile activity of fetal airway smooth muscle is not so surprising since the intestine and the lung have a common embryological origin, with the lung developing as an outgrowth of the foregut in the late embryonic stage (4). Nevertheless, it indicates that airway smooth muscle would need to lose its capacity to generate spontaneous electrical activity sometime during fetal life or at birth and acquire the characteristics of tonic smooth muscle. If and when this occurs is unknown.The phenomenon of spontaneous narrowing of airways in the fetal lung was first observed in explants of lung in culture from embryos of chicken (5) and guinea pigs (6). More recently it was reported in explants of first-trimester human lung (7) and in gestation Day 11 mouse lung (8), where by 48 h in culture, spontaneous contractions began. However, much less information is available for intact fetal airways. McCray (7) noted spontaneous activity of epithelial tubules in small fragments of fresh lungs from first-trimester human fetuses and characterized their contractile responses to pharmacologic agents (discussed later). Sparrow and colleagues (9, 10) video-recorded sequences of strong spontaneous narrowing of individual airways in the isolated intact bronchial tree in the late first and early second trimesters of fetal pig l...

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“…Unlike the cat, there was less variation in the angles of orientation at the lung periphery. The studies of SPARROW and coworkers [21,22], in which the airway smooth muscle was clearly identified using immunofluorescence and confocal microscopy, showed that, at least in foetal pigs, the airway smooth muscle assumes a predominantly transverse orientation in peripheral airways.…”

Section: Orientationmentioning

confidence: 99%

Airway smooth muscle in health and disease; methods of measurement and relation to function

James¹,

Carroll²

2000

Eur Respir J

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Smooth muscle is present and probably functional in the airways in utero and increases in absolute area during growth with little further change during adulthood. It encircles the entire airway below the level of the main bronchus, in a roughly circular orientation, except at high lung volumes. It occupies relatively more of the airway wall in the peripheral airways, reaching a maximum in the membranous bronchioles. Measurement of smooth muscle area in the airway wall is confounded by clinical classification of cases, methods of tissue retrieval and preparation, staining and orientation of sections, magnification, image analysis and statistical methods of comparison between groups. Airway smooth muscle area is pathologically increased in inflammatory conditions of the airways such as chronic obstructive pulmonary disease, in relation to airways obstruction, and asthma, in relation to severity and airway size (between 25 and 250% compared with control cases). It is increased in sudden infant death syndrome, but there are few studies in other conditions such as bronchiectasis. In asthma, smooth muscle must shorten (not necessarily to an abnormal degree) for the structural abnormalities of the airway to manifest as excessive airway narrowing. Not surprisingly there is renewed interest in the relationships between the mechanical and contractile properties of smooth muscle, parenchymal properties and lung volume and how these interact to determine smooth muscle length. The relative importance of smooth muscle area and mechanical properties, altered airway structure and airway inflammation in disease are yet to be determined.

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Foetal airway motor tone in prenatal lung development of the pig

Cited by 43 publications

References 14 publications

Innervation of Pulmonary Neuroendocrine Cells and Neuroepithelial Bodies in Developing Rabbit Lung

Innervation of Pulmonary Neuroendocrine Cells and Neuroepithelial Bodies in Developing Rabbit Lung

Spontaneous Peristaltic Airway Contractions Propel Lung Liquid through the Bronchial Tree of Intact and Fetal Lung Explants

Airway smooth muscle in health and disease; methods of measurement and relation to function

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