Migration and proliferation of guinea pig and human airway epithelial cells in response to tachykinins. Kim, John S., Klaus F. Rabe, Helgo Magnussen, Jonathan M. Green, and Steven R. White. Section of Pulmonary and Critical Care Medicine and Gwen Knapp Center for Lupus and Immunology Research, Department of Medicine, Division of Biological Sciences, University of Chicago, Chicago, Illinois; and the Krankenhaus Gro[beta]hansdorf, Zentrum f[umlaut]ur Pneumologie und Thoraxchirurgie, D-22927 Gro[beta]hansdorf, Germany.
APStracts 2:0057L, 1995.
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 de termined by immunohistochemistry after incorporation of the thymidine analog, bromodeoxyuridine (BrdU). Both GPTE and HBE cells migrated after stimulation with 10-11 M NKA (23.0 +/- 3.6 cells vs 5.4 +/- 1.2 per 10 high-power fields (hpf), P < 0.001, N = 8 for GPTE cells and 18.4 +/- 2.3 cells vs 3.8 +/- 0.5 cells per 10 hpf for control, P < 0.001, N = 4 for HBE cells). Migration was stimulated within 2 hr, was maximal after 6 hr and was attenuated substantially by the neurokinin-2 receptor antagonist SR 48968. NKA-stimulated migration was both chemokinetic and chemotactic, and 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. Migration was also stimulated by the specific neurokinin-1 receptor agonist Sar9-SP, though the magnitude of response was less than for NKA. Traversal of S-phase was stimulated in GPTE cells by Sar9-SP but not by NKA. Treatment with 10-10 M Sar9 -SP increased BrdU labelling from 2.7 +/- 0.7% to 12.1 +/- 3.6% of all cells (P < 0.05, N = 5). Stimulation with 10-10 M Sar9-SP for 72 hr increased cell numbers from 143,300 +/- 42,800 to 205,000 +/- 42,700 (P < 0.05, N = 3). We demonstrate that NKA and Sar9-SP elicit migration of GPTE cells in primary culture; however, only Sar9-SP elicits proliferation of these cells. These data suggest that tachykinins may facilitate repair of a damaged epithelium. 

Received 14 December 1994; accepted in final form 8 March 1995.
APS Manuscript Number L356-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.