Am. J. Respir. Cell Mol. Biol., Vol 12, No. 1, Jan 1995, 33-40.
Platelet-derived growth factor (PDGF)-AA, -AB, and -BB induce differential chemotaxis of early-passage rat lung fibroblasts in vitro
AR Osornio-Vargas, AL Goodell, NA Hernandez-Rodriguez, AR Brody, PG Coin, A Badgett and JC Bonner
Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Platelet-derived growth factor (PDGF) isoforms are chemoattractants and
mitogens for cells of mesenchymal origin that could be important mediators
of pulmonary fibrogenesis. We have previously reported that
particle-activated alveolar macrophages secrete homologues of PDGF that are
composed of all three PDGF isoforms (PDGF-AA, -AB, and -BB). This mixture
of macrophage-derived PDGF, once dissociated from the PDGF-
alpha-macroglobulin complex, induces chemotaxis of rat lung fibroblasts
(RLF) in the nanomolar range. In addition, we have reported that PDGF
isoforms induce differential proliferation of RLF (PDGF-BB > PDGF-AB
> PDGF-AA). In the present study, we sought to determine the relative
chemotactic potency of the three PDGF isoforms and correlate these
responses to the relative abundance of the two types of PDGF cell- surface
receptors: PDGF-alpha receptor (PDGF-R alpha) and PDGF-beta receptor
(PDGF-R beta). We also investigated the chemotactic activity of
combinations of two PDGF isoforms simultaneously. Isolates of early-
passage RLF were assayed for chemotaxis in 48-microwell chambers. Swiss
mouse 3T3 cells were assayed in parallel as a positive control cell line
for PDGF-R alpha and PDGF-R beta expression. RLF responded differentially
to the PDGF isoforms: PDGF-AB and PDGF-BB were potent chemoattractants and
stimulated maximal chemotactic responses between 4 and 8 ng/ml PDGF,
whereas PDGF-AA elicited a weak chemotactic response that was maximally 15%
of that obtained with either B-chain isoform. PDGF-AB and PDGF-BB were also
the most potent chemoattractants for Swiss 3T3 cells, and their response to
these B-chain isoforms was approximately 40% greater than that obtained for
RLF.(ABSTRACT TRUNCATED AT 250 WORDS)
