Divergent effects of extracellular oxygen on the growth, morphology, and function of human skin microvascular endothelial cells.
Partial pressure of extracellular oxygen influences a number of major cellular functions. The purpose of this study was to determine if the proliferation, morphology, and synthesis of proteins important in the function of skin microvascular endothelial cells were significantly altered by an extracellular oxygen tension used to culture endothelial cells. Microvascular endothelial cells were isolated from the dermis of neonatal foreskins and were studied at a venous capillary oxygen level (5% O(2), 38 mm Hg) and at an atmospheric oxygen level (20.8% O(2,) 158 mm Hg). At all time points studied and at all passage numbers, a significant inhibition of proliferation was observed at 20.8% O(2) compared to identical cultures grown and subcultured at 5% O(2). Two morphologically distinct endothelial cell populations were observed at 5% O(2). When mediators of angiogenesis and inflammation-such as basic fibroblast growth factor (bFGF), phorbol myristate acetate (PMA), and interleukin-1beta (IL-1beta)-were studied, additional differences in proliferation were observed. Atmospheric O(2) inhibited the synthesis of a major basement membrane protein (Type IV collagen), a major surface protein (PECAM-1), and increased the synthesis of von Willebrand factor (vWf). The rate of vascular channel formation induced by collagen gels was decreased at 5% O(2). These results demonstrate that an increase in extracellular oxygen tension from 5 to 20.8% can significantly alter the cellular physiology of human skin microvascular endothelial cells.
Zhou
L
L
Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
Dosanjh
A
A
Chen
H
H
Karasek
M
M
D001274:Atmospheric Pressure; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014841:von Willebrand Factor / Q000096:biosynthesis
D007375:Interleukin-1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen