Spontaneous Contraction of Pseudoglandular-Stage Human Airspaces Is Associated with the Presence of Smooth Muscle-α-Actin and Smooth Muscle-Specific Myosin Heavy Chain in Recently Differentiated Fetal Human Airway Smooth Muscle

Abstract

Background: Recent investigations demonstrating that pseudoglandular-stage airspaces contract spontaneously suggest that the production of contractile proteins by airway wall smooth muscle (ASM) is an important factor in the functional and structural differentiation of ASM. Aims: Ouraim was to determine if smooth muscle (SM)-myosin heavy chain (MHC) myofilaments, the ‘motor’ underlying SM contraction, and SM-α-actin myofilaments were distributed simultaneously in pseudoglandular-stage human lungs and to further define the nature of fetal airway contractions. Methods: Immunohistochemically stained sections of fetal lung (14 fetuses, 10.1–17 weeks gestation) were analysed by computer-assisted morphometry to determine airspace dimensions and detect SM-MHC- and SM-α-actin-ASM. Lung tissue from the same fetuses was also placed in explant culture to observe airway contractions using videomicroscopy. We found that the smallest airspaces were just as likely to be invested by a layer of SM-MHC-positive ASM as by a layer of SM-α-actin-positive ASM. In addition, larger airways or airways from more mature fetal lungs were more likely to be invested by either SM-MHC- or SM-α-actin-positive ASM. Spontaneous airspace contractions were peristalsis-like and variable in amplitude. The time interval between contractions was temperature dependent (mean ± SEM, 44 ± 7.5 s at 37°C), shortened by carbachol and increased by nitric oxide (NO)-donating drugs. Conclusions: These observations suggest that ASM differentiation is characterised by the simultaneous production of SM-α-actin and SM-MHC myofilaments and that the presence of these proteins is likely to be responsible for cholinergic- and NO-sensitive spontaneous contractions of fetal human airspaces.