Farber H W, Rounds S
Pulmonary Center, Boston University School of Medicine, Massachusetts 02118.
Exp Cell Res. 1990 Nov;191(1):27-36. doi: 10.1016/0014-4827(90)90031-5.
In a previous study, we found a marked difference in the release of a cytokine, neutrophil chemoattractant activity (NCA), from cultured endothelial cells exposed to acute decreases in ambient oxygen, depending on the vascular bed of origin. In the current study, we used this cytokine to evaluate the effect of long-term exposure to decreased oxygen on endothelial cell function. We found that, in aortic and pulmonary arterial endothelial cells maintained for months in decreased ambient oxygen (10 or 3% oxygen), exposure to acute decreases in ambient oxygen caused a change in the pattern of NCA release; however, the differential response between the two cell types persisted. Aortic endothelial cells release NCA when exposed acutely to a level of oxygen below that in which they have been chronically maintained. In contrast, pulmonary arterial endothelial cells release NCA only when exposed to 0% oxygen acutely, but only if grown chronically in 10% oxygen; otherwise there was no release of NCA. As another indicator of endothelial cell function, we evaluated the effects of acute hypoxic exposure on prostacyclin production by endothelial cells maintained in 21 or 3% oxygen. If grown in 21% oxygen, both cell types decreased prostacyclin production upon exposure to 0% oxygen. However, when grown in 3% oxygen, only aortic endothelial cells decreased prostacyclin production when exposed acutely to 0% oxygen; pulmonary arterial endothelial cell prostacyclin production did not change. This study demonstrating the persistence of a differential pattern of NCA release and the appearance of a differential pattern of prostacyclin production after a long-term decrease in environmental oxygen suggests that the capacity of certain vascular endothelial cells to respond to decreases in oxygen concentration is carried by the cell throughout its existence. Thus, in certain situations, vascular endothelial cells may be important in sensing acute decreases in ambient oxygen.
在之前的一项研究中,我们发现,暴露于环境氧急性降低状态下的培养内皮细胞释放一种细胞因子——中性粒细胞趋化活性(NCA)时,存在显著差异,这取决于血管床的来源。在当前研究中,我们使用这种细胞因子来评估长期暴露于低氧环境对内皮细胞功能的影响。我们发现,在环境氧降低(10%或3%氧气)状态下维持数月的主动脉和肺动脉内皮细胞,暴露于环境氧急性降低时,会导致NCA释放模式发生变化;然而,两种细胞类型之间的差异反应仍然存在。主动脉内皮细胞在急性暴露于低于其长期维持水平的氧时会释放NCA。相比之下,肺动脉内皮细胞仅在急性暴露于0%氧气时才会释放NCA,但前提是长期生长在10%氧气环境中;否则不会释放NCA。作为内皮细胞功能的另一个指标,我们评估了急性低氧暴露对在21%或3%氧气环境中维持的内皮细胞前列环素生成的影响。如果在21%氧气环境中生长,两种细胞类型在暴露于0%氧气时都会减少前列环素的生成。然而,当在3%氧气环境中生长时,只有主动脉内皮细胞在急性暴露于0%氧气时会减少前列环素的生成;肺动脉内皮细胞的前列环素生成没有变化。这项研究表明,在环境氧长期降低后,NCA释放的差异模式持续存在,前列环素生成的差异模式也出现了,这表明某些血管内皮细胞对氧浓度降低作出反应的能力在其整个生命周期中都存在。因此,在某些情况下,血管内皮细胞在感知环境氧的急性降低方面可能很重要。