Effects of neuropeptides on human lung fibroblast proliferation and chemotaxis.
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.
Harrison
N K
NK
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Dawes
K E
KE
Kwon
O J
OJ
Barnes
P J
PJ
Laurent
G J
GJ
Chung
K F
KF
D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology*; D015260:Neprilysin / Q000037:antagonists & inhibitors; D015288:Neurokinin A / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D006020:Glycopeptides; D009479:Neuropeptides; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D015288:Neurokinin A; D015260:Neprilysin; D015740:Calcitonin Gene-Related Peptide; C008890:phosphoramidon