TGF-beta 1 produces a "prooxidant" effect on bovine pulmonary artery endothelial cells in culture.
The pulmonary endothelium is known to be sensitive to oxidant injury, including that of hyperoxia. Similar to effects of exposure to 80-95% O2, porcine platelet transforming growth factor (TGF)-beta 1 at concentrations of greater than or equal to 0.3 ng/ml inhibited proliferation and caused enlargement of bovine pulmonary artery endothelial cells after 24 h of incubation in room air. Uptake of [3H]thymidine, but not of [3H]deoxycytidine, was suppressed by both hyperoxia and TGF-beta 1. The cellular enlargement produced by TGF-beta 1 in room air was attenuated in the presence of anoxia, indicating a need for O2 for TGF-beta 1 to have an effect on cell size. In the presence of 20 microM FeCl3, both TGF-beta 1 and 80% O2 produced marked cellular desquamation from culture dishes. The antioxidants dimethyl sulfoxide and vitamin E partially counteracted the growth inhibitory effect of TGF-beta 1 on endothelial cells. In contrast to its effect on endothelial cells, TGF-beta 1 only moderately altered size and proliferation of smooth muscle cells from the same pulmonary vessels. Uptake of [3H]thymidine by smooth muscle cells was uninfluenced in 48 h by TGF-beta 1, and little, if any, desquamation of these cells occurred with TGF-beta 1 in the presence of 20 microM FeCl3. We propose from these experiments that TGF-beta 1 may produce an oxidant effect on vascular endothelium that is capable of causing injury to this tissue.
Department of Medicine, New England Medical Center, Boston, Massachusetts 02111.
S K
SK
Das
B L
BL
Fanburg
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005290:Ferric Compounds / Q000494:pharmacology; D000860:Hypoxia / Q000473:pathology; D010084:Oxidation-Reduction; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D002712:Chlorides; D005290:Ferric Compounds; D016212:Transforming Growth Factor beta; C024555:ferric chloride; D004121:Dimethyl Sulfoxide