Early-passage rat lung fibroblasts do not migrate in vitro to transforming growth factor-beta.
Lung fibrosis has been postulated to be mediated by the production of macrophage-derived growth factors that are both mitogenic and chemotactic for fibroblasts. In vitro studies from our laboratory demonstrated that alveolar and interstitial macrophages treated with iron and asbestos release platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) into the media. This conditioned media was capable of inducing proliferation and chemotaxis of primary rat lung fibroblasts (RLF). TGF-beta is known to be present in the media, and RLF have high-affinity receptors for TGF-beta. However, we found that > 95% of the chemotaxis was blocked by a polyclonal anti-PDGF antibody, whereas anti-TGF-beta did not change cell migration. TGF-beta has been described previously as a potent chemoattractant for fibroblasts. Thus, we tested the potential of purified TGF-beta to induce RLF chemotaxis in an attempt to address this apparent contradiction in results. Four separate preparations of RLFs from four different rats, Swiss 3T3 cells, human and rat fetal skin fibroblasts, and human foreskin fibroblasts were tested for chemotaxis using purified porcine TGF-beta 1 as well as human TGF-beta. None of these cells responded chemotactically to TGF-beta over a broad range of concentrations used (0.004 pg/ml to 50 ng/ml). RLF plated at different densities also did not respond to TGF-beta. On the other hand, all the fibroblast types migrated vigorously to PDGF (4 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Osornio-Vargas
A R
AR
Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
Kalter
V G
VG
Badgett
A
A
Hernández-Rodríguez
N
N
Aguilar-Delfín
I
I
Brody
A R
AR
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002633:Chemotaxis; D002634:Chemotaxis, Leukocyte; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D008168:Lung / Q000166:cytology*; D008297:Male; D051379:Mice; D009000:Monocytes / Q000166:cytology; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta; D013936:Thymidine