AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 1 119-L126, Copyright © 1995 by American Physiological Society
Migration and proliferation of guinea pig and human airway epithelial cells in response to tachykinins
J. S. Kim, K. F. Rabe, H. Magnussen, J. M. Green and S. R. White
Section of Pulmonary and Critical Care Medicine, University of Chicago, Illinois 60637, USA.
Restoration of the epithelial lining of a damaged airway is a necessary
component of airway repair. Tachykinins, including substance P (SP) and
neurokinin A (NKA), are localized to sensory nerves within the airway
mucosa. These tachykinins regulate several airway functions, but their role
in the repair of the epithelium has not been explored. To determine whether
tachykinins stimulate migration and proliferation of airway epithelial
cells, guinea pig tracheal epithelial (GPTE) and human bronchial epithelial
(HBE) cells were grown in primary culture for 4-5 days. Epithelial cell
migration was assessed in a blindwell chemotaxis chamber, and proliferation
was determined by immunohistochemistry after incorporation of the thymidine
analogue 5-bromo-2'-deoxyuridine (BrdU). Both GPTE and HBE cells migrated
after stimulation with 10(-11) M NKA [23.0 +/- 3.6 vs. 5.4 +/- 1.2 cells
per 10 high-power fields (hpf), P < 0.001, n = 8 for GPTE cells; 18.4
+/- 2.3 vs. 3.8 +/- 0.5 cells per 10 hpf for control, P < 0.001, n = 4
for HBE cells]. Migration was stimulated within 2 h, was maximal after 6 h,
and was attenuated substantially by the neurokinin 2 (NKA)-receptor
antagonist SR-48968. NKA-stimulated migration was both chemokinetic and
chemotactic, and it could be blocked by inhibition of protein synthesis
with cyclohexamide, inhibition of microtubular function with colchicine, or
inhibition of actin microfilament elongation with cytochalasin D.(ABSTRACT
TRUNCATED AT 250 WORDS)
