Maximal pdgf-induced lung fibroblast chemotaxis requires the pdgf
[alpha]-receptor.
Osornio-Vargas, Alvaro R., Pamela M. Lindroos, Patrick G. Coin,
Annette Badgett, Norma A. Hernandez-Rodriguez, and James C. Bonner.
Laboratory of Pulmonary Pathobiology,National Institute of
Environmental Health Sciences, Research Triangle Park, NC 27709 USA,
Veterans Administration Hospital, Durham, NC 27705 USA and Division
of Basic Investigation, National Cancer Institute, Mexico D.F.
14000
APStracts 3:0034L, 1996.
Alteration of the Platelet-derived growth factor (PDGF) receptor
system could be important in enhancing the mitogenic and chemotactic
potential of lung fibroblasts during pulmonary fibrogenesis. We
previously reported that interleukin-1[beta] (IL-1[beta]) upregulates
the PDGF [alpha]-receptor (PDGF-R[alpha]) gene and in this study we
sought to establish the importance of the PDGF-R[alpha] relative to
the PDGF-R[beta] in mediating a chemotactic reponse to PDGF-AA, -AB
and -BB. Pretreatment of fibroblasts for 24 hr with IL-1[beta]
increased chemotaxis to all three PDGF isoforms. IL-1[beta]
pretreatment markedly increased the maximal number of [125I]PDGF-AA
binding sites, but did not change the number of [125I]PDGF-AB or
PDGF-BB sites. However, IL-1[beta] increased [125I]PDGF-AB affinity
two-fold. Neomycin (5 mM) was used as a PDGF-R[alpha] antagonist and
completely blocked [125I]PDGF-AA binding and PDGF-AA-induced
chemotaxis. The binding affinity of [125I]PDGF-AB and [125I]PDGF-BB
was increased 2 to 3-fold by neomycin, and chemotaxis to PDGF-AB and
PDGF-BB was enhanced. These results define a role for the PDGF
-R[alpha] as a regulatory receptor subtype that is necessary for PDGF
isoforms to exert maximal chemotaxis.
Received 20 November 1995; accepted in final form 13 February
1996.
APS Manuscript Number L338-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96