Development of the innervation and airway smooth muscle in human fetal lung

Human and porcine fetal airways have been shown to contract spontaneously f rom the first trimester, the latter also contracting in response to neural stimulation. Our object was to map immunohistochemically the innervation an d its relationship to the airway smooth muscle (ASM) in the human fetal lun g from early gestation to the postnatal period. Whole mounts of the bronchi al tree were stained with antibodies to the pan-neuronal marker protein gen e product 9.5, the Schwann cell marker S-100, and the ASM contractile prote in cr-actin, and imaged using confocal microscopy. By the end of the embryo nic period (53 d gestation), the branching epithelial tubules in the primor dial lung were covered with ASM to the base of the terminal sacs. An extens ive plexus of nerve trunks containing nerve bundles, forming ganglia, and S chwann cells ensheathed the ASM. By 16 wk (canalicular stage), maturation o f the innervation was advanced with two major nerve trunks running the leng th of the bronchial tree, giving rise to varicosed fibers lying on the ASM, An extensive nerve plexus in the mucosa was also present. The distal airwa ys of infants who had died of Sudden Infant Death Syndrome were also covere d with smooth muscle and were well innervated. Thus, an essentially complet e coat of ASM and an abundant neural plexus ensheathing the airways are an integral part of the branching epithelial tubules from early in lung develo pment.