In vivo restitution of airway epithelium.
Epithelial shedding occurs in health and, extensively, in inflammatory airway diseases. This study describes deepithelialisation, reepithelialisation and associated events in guinea-pig trachea after shedding-like epithelial denudation in vivo. Mechanical deepithelialisation of an 800-microns wide tracheal zone was carried out using an orotracheal steel probe without bleeding or damage to the basement membrane. Reepithelialisation was studied by scanning- and transmission electron microscopy and light microscopy. Nerve fibres were examined by immunostaining. Cell proliferation was analysed by [3H]-thymidine autoradiography. Immediately after epithelial removal secretory and ciliated (and presumably basal) epithelial cells at the wound margin dedifferentiated, flattened and migrated rapidly (2-3 microns/min) over the denuded basement membrane. Within 8-15 h a new, flattened epithelium covered the entire deepithelialised zone. At 30 h a tight epithelial barrier was established and after 5 days the epithelium was fully redifferentiated. After completed migration an increased mitotic activity occurred in the epithelium and in fibroblasts/smooth muscle beneath the restitution zone. Reinnervating intraepithelial calcitonin gene-related peptide-containing nerve fibres appeared within 30 h. We conclude that (1) reproducible shedding-like denudation, without bleeding or damage to the basement membrane, can be produced in vivo; (2) secretory and ciliated cells participate in reepithelialisation by dedifferentiation and migration; (3) the initial migration is very fast in vivo; (4) shedding-like denudation may cause strong secretory and exudative responses as well as proliferation of epithelium, and fibroblasts/smooth muscle. Rapid restitution of airway epithelium may depend on contributions from the microcirculation and innervation.
Erjefält
J S
JS
Department of Medical Cell Research, University of Lund, Sweden.
Erjefält
I
I
Sundler
F
F
Persson
C G
CG
D000818:Animals; D001485:Basement Membrane / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation; D002465:Cell Movement; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D008938:Mitosis / Q000502:physiology; D009092:Mucous Membrane / Q000502:physiology; D013997:Time Factors; D014132:Trachea / Q000166:cytology / Q000294:innervation / Q000502:physiology*; D014140:Tracheotomy; D014945:Wound Healing / Q000502:physiology