Vaudaux P, Waldvogel F A
J Infect Dis. 1980 Oct;142(4):586-93. doi: 10.1093/infdis/142.4.586.
Factors contributing to the binding and reversible inactivation of gentamicin by purulent exudates were studied in a simplified in vitro model consisting of purified human polymorphonuclear leukocytes (PMNLs). Whereas intact PMNLs (10(6)-10(8)/ml) bound almost no [14C]gentamicin, freeze-thawed PMNLs showed extensive [14C]gentamicin binding, expressed as antibiotic cosedimenting with particulate material from the lysed PMNLs. Antibiotic binding could be related to the concentration of lysed PMNLs and to the amount of [14C]gentamicin added. Binding of [14C]gentamicin by lysed PMNLs was highly sensitive to DNase I but was unaffected by RNase, Triton X-100, or protease. Purified chromatin or DNA from either purulent exudates or lysed PMNLs reproduced the [14C]gentamicin-binding pattern obtained with crude PMNL lysate. These results show that gentamicin inactivation in purulent exudates can be correlated with binding of the antibiotic to lysed PMNLs; PMNL chromatin DNA is identified as one of the major binding factors.
在一个由纯化的人多形核白细胞(PMNLs)组成的简化体外模型中,研究了导致庆大霉素被脓性渗出物结合和可逆失活的因素。完整的PMNLs(10⁶ - 10⁸/ml)几乎不结合[¹⁴C]庆大霉素,而冻融的PMNLs则显示出广泛的[¹⁴C]庆大霉素结合,表现为抗生素与裂解的PMNLs中的颗粒物质共沉淀。抗生素结合可能与裂解的PMNLs的浓度以及添加的[¹⁴C]庆大霉素的量有关。裂解的PMNLs对[¹⁴C]庆大霉素的结合对脱氧核糖核酸酶I高度敏感,但不受核糖核酸酶、曲拉通X - 100或蛋白酶的影响。来自脓性渗出物或裂解的PMNLs的纯化染色质或DNA重现了用粗PMNL裂解物获得的[¹⁴C]庆大霉素结合模式。这些结果表明,脓性渗出物中庆大霉素的失活可能与抗生素与裂解的PMNLs的结合有关;PMNL染色质DNA被确定为主要结合因子之一。