Hyperoxia increases plasminogen activator activity of cultured endothelial cells.
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.
Phillips
P G
PG
Department of Veterans Affairs Medical Center, Albany, New York.
Birnby
L
L
Di Bernardo
L A
LA
Ryan
T J
TJ
Tsan
M F
MF
D000818:Animals; D002364:Caseins / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D003470:Culture Media; D010450:Endopeptidases / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D010100:Oxygen / Q000494:pharmacology*; D010960:Plasminogen Activators / Q000378:metabolism*; D016608:Talin / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
D002364:Caseins; D003470:Culture Media; D016326:Extracellular Matrix Proteins; D016608:Talin; D016596:Vinculin; D010450:Endopeptidases; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D010100:Oxygen