Feldman C, Anderson R, Theron A J, Ramafi G, Cole P J, Wilson R
Department of Medicine, Johannesburg Hospital, South Africa.
Inflammation. 1997 Dec;21(6):655-65. doi: 10.1023/a:1027342424205.
The effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the beat frequency and structural integrity of human ciliated respiratory epithelium were studied in vitro, in the presence or absence of polymorphonuclear leukocytes (PMNL), the antimicrobial agents, roxithromycin, clarithromycin, and azithromycin and the antioxidative enzymes catalase and superoxide dismutase (SOD). All three PL caused dose-dependent slowing of ciliary beat frequency (CBF) and epithelial damage (ED) at concentrations > or = 1 microgram/ml, which were unaffected by inclusion of the antimicrobial agents and antioxidative enzymes. When epithelial strips were exposed to the combination of PMNL and PL, there was significant potentiation of ciliary dysfunction and ED, which was ameliorated by pretreatment of the PMNL with the antimicrobial agents or by inclusion of catalase, but not SOD. These results demonstrate that LPC, PAF, and lyso-PAF cause epithelial damage by direct mechanisms which are oxidant-independent, as well as by indirect mechanisms involving phagocyte-derived reactive oxidants. Macrolides and azalide antimicrobial agents may have beneficial effects on airway inflammation in asthma and microbial infections by protecting ciliated epithelium against oxidative damage inflicted by PL-sensitized phagocytes.
在体外研究了生物活性磷脂（PL）、血小板活化因子（PAF）、溶血PAF和溶血磷脂酰胆碱（LPC）对人纤毛呼吸上皮的搏动频率和结构完整性的影响，实验条件为存在或不存在多形核白细胞（PMNL）、抗菌剂罗红霉素、克拉霉素和阿奇霉素以及抗氧化酶过氧化氢酶和超氧化物歧化酶（SOD）。所有三种PL在浓度≥1微克/毫升时均引起纤毛搏动频率（CBF）剂量依赖性减慢和上皮损伤（ED），抗菌剂和抗氧化酶的加入对此无影响。当上皮条暴露于PMNL和PL的组合时，纤毛功能障碍和ED有显著增强，用抗菌剂预处理PMNL或加入过氧化氢酶可改善这种情况，但加入SOD则不能。这些结果表明，LPC、PAF和溶血PAF通过与氧化剂无关的直接机制以及涉及吞噬细胞衍生的活性氧化剂的间接机制导致上皮损伤。大环内酯类和氮杂内酯类抗菌剂可能通过保护纤毛上皮免受PL致敏吞噬细胞造成的氧化损伤，对哮喘和微生物感染中的气道炎症产生有益影响。
