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Published ahead of print on October 22, 2004, doi:10.1164/rccm.200408-1046OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 3, February 2005, 217-223

A more recent version of this article appeared on February 1, 2005
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Submitted on August 17, 2004
Accepted on October 18, 2004

{beta}1 Integrins Mediate Enhancement of Airway Smooth Muscle Proliferation by Collagen and Fibronectin

Trang T-B Nguyen1, Jeremy P.T. Ward1, and Stuart J Hirst1*

1 Department of Asthma, Allergy and Respiratory Science, The Guy's, King's and St. Thomas' School of Medicine, King's College London, London, United Kingdom

* To whom correspondence should be addressed. E-mail: stuart.hirst{at}kcl.ac.uk.

Airway smooth muscle (ASM) accumulation and enrichment of the extracellular matrix (ECM) with type I collagen and fibronectin are major pathological features of airway remodeling in asthma. These ECM components confer enhanced ASM proliferation in vitro but a requirement for specific integrin ECM receptors has not been examined. Here, we examined the mitogen, platelet-derived growth factor (PDGF)-BB on {beta}1-integrin expression on human ASM cells cultured on these ECM substrates and defined the involvement of specific integrins in cell attachment and proliferation using integrin-neutralizing antibodies. PDGF-BB-dependent proliferation was enhanced 2- to 3-fold by monomeric type I collagen or fibronectin and to a lesser extent by vitronectin; other interstitial ECM components (fibrillar type I and III collagen and tenascin-C) had no effect. Excepting increased {alpha}3 expression induced by PDGF-BB and monomeric type I collagen or fibronectin, {alpha}1, {alpha}2, {alpha}4, {alpha}5, {alpha}v and {alpha}v{beta}3 integrins were unchanged compared with unstimulated cells on plastic. Blocking antibodies revealed {alpha}2{beta}1 and {alpha}v{beta}3 mediated attachment to monomeric type I collagen, whereas attachment to fibronectin required {alpha}5{beta}1. In contrast, enhancement of PDGF-BB-dependent proliferation by either monomeric type I collagen or fibronectin required {alpha}2{beta}1, {alpha}4{beta}1 and {alpha}5{beta}1 integrins. These data suggest multiple {beta}1-integrins regulate enhanced ASM proliferative responses.


Key words: Asthma, airway remodeling, airway smooth muscle, proliferation, extracellular matrix




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