Dynamics of tgf-[beta]3 peptide activity during rat alveolar
epithelial cell proliferative recovery from acute hyperoxia.
Buckley, Sue, Kim Chi Bui, Mukkaram Hussain, and David Warburton.
Departments of Surgery & Pediatrics, Childrens Hospital Los
Angeles Research Institute, U.S.C. School of Medicine, 4650 Sunset
Boulevard, Los Angeles, CA 90027
APStracts 3:0022L, 1996.
Hyperoxia causes a reproducible pattern of lung injury and recovery,
characterized by proliferation of type 2 alveolar epithelial cells
(AEC2) during the recovery phase. We measured TGF-[beta] peptide
production by AEC2 and macrophages from lungs of adult male rats
exposed to 100% oxygen for 48 hr and then allowed to recover for up
to 72 hr in room air. TGF-[beta] peptide activity levels were
measured using the PAI-1 promoter-luciferase mink lung epithelial
cell assay and characterized with peptide specific inhibitory
antibodies. Control AEC2 produced 997+54 pg active TGF-[beta]/106
cells/24 hr (X+SD), of which >70% was TGF-[beta]3, while
cultured macrophages produced 58+17 pg active TGF-[beta]/106
macrophages/24hr, >80% of which was TGF-[beta]1. During
hyperoxia and recovery, active TGF-[beta]3 production by AEC2
decreased by 75%, with a nadir at 24 hr recovery (P<0.005). In
contrast, TGF-[beta] peptide activity increased from undetectable
levels in lung lavage from control rats, to a peak of 1470+743 pg/
rat after 48 hr oxygen exposure and 24 hr recovery, while lavaged
macrophage TGF-[beta] production in culture also increased 3-fold to
a peak of 150+5 pg/106 cells/24 hr following 48 hr oxygen exposure
(P<0.005). The nadir of active TGF-[beta]3 production by AEC2
coincided with the peak of the AEC2 proliferative phase of repair as
determined by BrdU incorporation and FACS analysis of freshly
isolated AEC2. We conclude that active TGF-[beta]3 production by AEC2
is dynamically down-regulated during the proliferative phase of
recovery from acute hyperoxic injury in rat. We speculate that
decreased autocrine negative regulation of AEC2 proliferation by TGF
-[beta]3 may facilitate AEC2 proliferation during recovery from acute
hyperoxic injury.
Received 28 August 1995; accepted in final form 15 January 1996.
APS Manuscript Number L260-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96