Postnatal remodeling of the neural components of the epithelial- mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen

Shawnessy D. Larson, Edward S Schelegle, William F. Walby, Laurel J Gershwin, Michelle V. Fanuccihi, Michael J. Evans, Jesse P. Joad, Brian K. Tarkington, Dallas M. Hyde, Charles Plopper

Research output: Contribution to journalArticle

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Abstract

Nerves and neuroendocrine cells located within the airway epithelium are ideally situated to sample a changing airway environment, to transmit that information to the central nervous system, and to promote trophic interactions between epithelial and mesenchymal cellular and acellular components. We tested the hypothesis that the environmental stresses of ozone (O3) and house dust mite allergen (HDMA) in atopic infant rhesus monkeys alter the distribution of airway nerves. Midlevel bronchi and bronchioles from 6-month-old infant monkeys that inhaled filtered air (FA), house dust mite allergen HDMA, O3, or HDMA + O3 for 11 episodes (5 days each, 0.5 ppm O3, 8 h/day followed by 9 days recovery) were examined using immunohistochemistry for the presence of Protein gene product 9.5 (PGP 9.5), a nonspecific neural indicator, and calcitonin gene-related peptide (CGRP). Along the axial path between the sixth and the seventh intrapulmonary airway generations, there were small significant (P < 0.05) decrements in the density of epithelial nerves in monkeys exposed to HDMA or O3, while in monkeys exposed to HDMA + O3 there was a greater significant (P < 0.05) reduction in epithelial innervation. In animals exposed to O3 or HDMA + O3 there was a significant increase in the number of PGP 9.5 positive/CGRP negative cells that were anchored to the basal lamina and emitted projections in primarily the lateral plain and often intertwined with projections and cell bodies of other similar cells. We conclude that repeated cycles of acute injury and repair associated with the episodic pattern of ozone and allergen exposure alter the normal development of neural innervation of the epithelial compartment and the appearance of a new population of undefined PGP 9.5 positive cells within the epithelium.

Original languageEnglish (US)
Pages (from-to)211-220
Number of pages10
JournalToxicology and Applied Pharmacology
Volume194
Issue number3
DOIs
StatePublished - Feb 1 2004

Fingerprint

Dermatophagoides Antigens
Ozone
Macaca mulatta
Allergens
Haplorhini
Calcitonin Gene-Related Peptide
Epithelium
Cells
Bronchioles
Neuroendocrine Cells
Proteins
Neurology
Bronchi
Basement Membrane
Animals
Repair
Central Nervous System
Immunohistochemistry
Air
Neurons

Keywords

  • Allergen exposure
  • HDMA
  • Ozone

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Postnatal remodeling of the neural components of the epithelial- mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen. / Larson, Shawnessy D.; Schelegle, Edward S; Walby, William F.; Gershwin, Laurel J; Fanuccihi, Michelle V.; Evans, Michael J.; Joad, Jesse P.; Tarkington, Brian K.; Hyde, Dallas M.; Plopper, Charles.

In: Toxicology and Applied Pharmacology, Vol. 194, No. 3, 01.02.2004, p. 211-220.

Research output: Contribution to journalArticle

Larson, Shawnessy D. ; Schelegle, Edward S ; Walby, William F. ; Gershwin, Laurel J ; Fanuccihi, Michelle V. ; Evans, Michael J. ; Joad, Jesse P. ; Tarkington, Brian K. ; Hyde, Dallas M. ; Plopper, Charles. / Postnatal remodeling of the neural components of the epithelial- mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen. In: Toxicology and Applied Pharmacology. 2004 ; Vol. 194, No. 3. pp. 211-220.
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