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 cellu lar functions. The purpose of this study was to determine if the proliferat ion, morphology, and synthesis of proteins important in the function of ski n microvascular endothelial cells were significantly altered by an extracel lular oxygen tension used to culture endothelial cells. Microvascular endot helial cells were isolated from the dermis of neonatal foreskins and were s tudied at a venous capillary oxygen level (5% O-2, 38 mm Hg) and at an atmo spheric 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 obse rved at 20.8% O-2 compared to identical cultures grown and subcultured at 5 % O-2. Two morphologically distinct endothelial cell populations were obser ved at 5% O-2. When mediators of angiogenesis and inflammation-such as basi c fibroblast growth factor (bFGF), phorbol myristate acetate (PMA), and int erleukin-1 beta (IL-1 beta)-were studied, additional differences in prolife ration were observed. Atmospheric O-2 inhibited the synthesis of a major ba sement 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 tensi on from 5 to 20.8% can significantly alter the cellular physiology of human skin microvascular endothelial cells. J. Cell. Physiol. 182:134-140, 2000. (C) 2000 Wiley-Liss, Inc.