New pathogenesis and therapeutic : strategy for diffuse panbronchiolitis by regulation of intracellular apoptotic molecules

1)弥漫性泛细支气管炎(DPB)患者呼吸性细支气管区周围淋巴细胞未见Bax表达，而大部分淋巴细胞表达Bcl2。此外，细胞凋亡诱导酶caspase3也未被染色。这表明Bcl2蛋白的过度表达在抑制DPB14或15元环大环内酯类抗生素的淋巴细胞凋亡中起重要作用。2)L通过下调抗凋亡蛋白Bclxl诱导CD_3/CD_(28)活化的健康志愿者淋巴细胞发生凋亡。3)在慢性铜绿假单胞菌感染小鼠模型中，给予14元大环内酯类抗生素80天后，红霉素抑制铜绿假单胞菌生物被膜的形成，随后消除细菌。这是首次报道，表明在体内长期治疗大环内酯类药物可以通过破坏生物膜的形成来消除细菌。

1)No immunostain of Bax was observed in lymphocytes around respiratory bronchioles of diffuse panbronchiolitis (DPB), while Bcl-2 was stained in the majority of the lymphocytes. Furthermore, apoptosis-inducing enzyme, caspase 3 was also unstained. This indicates that over expression of Bcl-2 protein plays an important role in suppression of lymphocyte apoptosis in DPB.2)14- or 15-membered ring macrolide antibiotics at 100 mg/l induced apoptosis of CD3/CD28-activated lymphocytes obtained from healthy volunteers through downregulation of anti-apoptotic protein, Bcl-xL. This suggest that macrolides influence intracellular signal, especially anti-apoptotic protein.3)In a murine model with chronic Pseudomonas aeruginosa infection, 80-day administration of 14-membered macrolide antibiotic, erythromycin inhibited the biofilm formation of P.aeruginosa followed by elimination of the bacteria. This is a first report, indicating in vivo that long-term treatment of macrolides can eliminate the bacteria through destruction of biofilm formation.