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Immunohistochemical localization of peptide-containing nerves in human airways: age-related changes
A A Hislop1, J Wharton, K M Allen
1Institute of Child Health, London, United Kingdom.
Insights
Human airway innervation changes with age. While most nerve markers remain constant from infancy to adulthood, peptide-containing nerves decrease in adult bronchioli, with vasoactive intestinal polypeptide nerves increasing in smooth muscle.
Area of Science:
- Pulmonary Medicine
- Neuroscience
- Developmental Biology
Background:
- Bronchial reactivity exhibits developmental changes, suggesting alterations in neural control mechanisms.
- Understanding the maturation of airway innervation is crucial for comprehending respiratory control development.
Purpose of the Study:
- To investigate age-related changes in the distribution and relative number of nerve fibers in the human intrapulmonary airways.
- To characterize specific neuropeptide-containing nerve subpopulations within the developing and adult airway.
Main Methods:
- Autopsy lung tissue from infants (0-3.5 yr), children (8.3-10.75 yr), and adults (17-24 yr) was analyzed.
- Indirect immunofluorescence was employed to detect general neuronal markers (PGP 9.5, synaptophysin) and neuropeptide-specific markers (NPY, VIP, SST, SP, CGRP, TH).
Main Results:
- The distribution and relative number of general neuronal markers and most neuropeptide-containing nerves remained consistent across age groups.
- Neuropeptide tyrosine (NPY)-immunoreactive nerves were the most abundant, innervating smooth muscle, glands, cartilage, and submucosa.
- Two age-related differences were observed: fewer peptide-containing nerves in adult bronchioli/respiratory units, and a greater relative number of vasoactive intestinal polypeptide (VIP)-containing nerves in bronchial/bronchiolar smooth muscle in older individuals.
Conclusions:
- Airway innervation undergoes specific developmental modifications, particularly concerning peptide-containing nerve populations.
- The increased relative number of VIP nerves in smooth muscle of older individuals suggests a role in modulating airway tone during maturation.
- Further research into peptide receptor development in the airway is warranted to elucidate these age-related changes.
Abstract:
Bronchial reactivity changes during childhood, indicating possible changes in neural control. Nerves supplying the intrapulmonary airways were therefore studied in autopsy tissue from 14 normal infants (0 to 3.5 yr), 3 children (8.3 to 10.75 yr), and 4 adults (17 to 24 yr). An indirect immunofluorescence technique was used to study the distribution and relative number of nerve fibers containing the general neuronal markers protein gene product 9.5 and synaptophysin. Nerve subpopulations were identified using antisera to neuropeptide tyrosine, vasoactive intestine polypeptide, somatostatin, substance P, calcitonin gene-related peptide, and the enzyme tyrosine hydroxylase. Between birth and 3 yr, the distribution and relative number of immunoreactive nerves shown by both the general neuronal markers and specific antisera did not change. Neuropeptide tyrosine-immunoreactive nerves were the most common peptide-containing nerve subpopulation identified in the human lung, supplying bronchial smooth muscle, submucosal glands, cartilage, and submucosa. Other peptide-containing nerves exhibited distinct distribution patterns. Two differences in the airway innervation were identified between cases aged 0 to 3.5 yr and the older age groups. Relatively fewer peptide-containing nerves occurred in the adult bronchioli and respiratory unit, but the relative number of vasoactive intestinal polypeptide-containing nerves supplying the bronchial and bronchiolar smooth muscle was greater in the two older age groups. Given these apparent age-related differences in the number of peptide-containing nerves supplying the human airway, studies on the development of peptide receptors are indicated.