AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 278-L283, Copyright © 1995 by American Physiological Society
Effects of neuropeptides on human lung fibroblast proliferation and chemotaxis
N. K. Harrison, K. E. Dawes, O. J. Kwon, P. J. Barnes, G. J. Laurent and K. F. Chung
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
An increase in subepithelial mesenchymal cells and associated connective
tissue is a feature of bronchial asthma. We determined whether
neuropeptides could modulate fibroblast activity, particularly with respect
to proliferation and chemotaxis. Human lung fibroblasts were cultured with
neurokinin A (NKA), substance P (SP), vasoactive intestinal peptide (VIP),
and calcitonin-gene-related peptide (CGRP). After 48 h, fibroblast
proliferation was measured by a colorimetric assay based on the uptake and
subsequent release of methylene blue. The chemotactic response to
neuropeptides was determined with the use of a modified Boyden chamber.
Both NKA and SP (10(-7)-10(-4) M) stimulated human lung fibroblast
proliferation in HFL1 and IMR-90 fibroblasts. VIP and CGRP had no effect on
fibroblast proliferation. NKA alone stimulated fibroblast chemotaxis
maximally at 10(-10) M. Neutral endopeptidase (NEP) activity of 0.52 and
5.2 pmol/10(6) cells was assayed in IMR-90 and Hs68 fibroblasts,
respectively. Phosphoramidon (5 x 10(-6)-10(-5) M), an NEP inhibitor,
enhanced fibroblast proliferation in a dose-dependent manner. Thus
neuropeptides have the potential to cause activation of mesenchymal cells,
and neuropeptide release may contribute to the structural abnormalities
observed in asthmatic airways.
