AJP - Lung Cellular and Molecular Physiology, Vol 262, Issue 1 21-L31, Copyright © 1992 by American Physiological Society
Hyperoxia increases plasminogen activator activity of cultured endothelial cells
P. G. Phillips, L. Birnby, L. A. Di Bernardo, T. J. Ryan and M. F. Tsan
Department of Veterans Affairs Medical Center, Albany, New York.
Confluent calf pulmonary artery endothelial monolayers exposed to 95%
oxygen for 1, 2, or 3 days exhibit a time-dependent increase in adherence
to substratum, which closely parallels changes in actin cytoarchitecture
and the distribution of focal contact proteins vinculin and talin. Oxygen
exposure also resulted in elevated plasminogen activator (PA) activity in
conditioned media (CM) and in cytoskeletal protein- and focal contact
protein-enriched fractions, with highest levels achieved in the latter two
fractions at 48 h after oxygen exposure. PAs have been shown to participate
in dismantling of extracellular matrix in a number of physiological and
pathological situations. Immunocytochemical studies demonstrated extensive
restructuring of matrix proteins collagen IV, laminin, and fibronectin,
which correlated temporally with elevated PA levels. Further, when
protease-containing cell fractions were used to study degradation of
isolated matrices, those obtained from hyperoxia-exposed cells were
substantially more active than those from normoxia-exposed cells. Our data
suggest that hyperoxia-induced production of PA (and perhaps other
proteases) may be partly responsible for degradation of the extracellular
matrix of endothelial cells.
