Sommers Smith Sally K, Smith Dennis M
College of General Studies, Boston University, Massachusetts 02215, USA.
In Vitro Cell Dev Biol Anim. 2002 May;38(5):298-304. doi: 10.1290/1071-2690(2002)038<0298:BBIAIC>2.0.CO;2.
Continuous beta blockade stimulates deposition of collagen in the pulmonary alveolar interstitium of adult rats. It also causes changes to the capillary endothelial cell compartment reminiscent of programmed cell death. To test whether beta blockade results in endothelial cell apoptosis, cultures of capillary endothelial cells were treated with both a wide-spectrum beta blocker and a beta-2-specific antagonist. Apoptosis was measured in these cultures using both terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling and annexin-V assays. Both forms of beta blockade stimulated programmed cell death in these cultures. To test whether the apoptotic effect of beta blockade was related to interstitial collagen deposition, capillary endothelial cells were cocultured with beta-blocked pulmonary fibroblast monolayers. Cocultured endothelial cells were substantially protected from apoptosis after beta blockade; coculture over plain tissue culture plastic or over exogenous collagen films had no effect on programmed cell death in endothelial cells. These results suggest that both pulmonary endothelial and interstitial cells are vulnerable to injury from beta blockade but that paracrine interactions between these cells may protect the peripheral lung from substantive damage.
持续的β受体阻滞剂刺激成年大鼠肺泡间质中胶原蛋白的沉积。它还会引起毛细血管内皮细胞区室的变化，类似于程序性细胞死亡。为了测试β受体阻滞剂是否会导致内皮细胞凋亡，用一种广谱β受体阻滞剂和一种β2特异性拮抗剂处理毛细血管内皮细胞培养物。使用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法和膜联蛋白-V检测法在这些培养物中测量细胞凋亡。两种形式的β受体阻滞剂都刺激了这些培养物中的程序性细胞死亡。为了测试β受体阻滞剂的凋亡作用是否与间质胶原蛋白沉积有关，将毛细血管内皮细胞与经β受体阻滞剂处理的肺成纤维细胞单层共培养。β受体阻滞剂处理后，共培养的内皮细胞基本免受凋亡；在普通组织培养塑料或外源性胶原膜上共培养对内皮细胞的程序性细胞死亡没有影响。这些结果表明，肺内皮细胞和间质细胞都容易受到β受体阻滞剂的损伤，但这些细胞之间的旁分泌相互作用可能保护外周肺免受实质性损伤。
