Synergistic and additive killing by antimicrobial factors found in human airway surface liquid
Synergistic and additive killing by antimicrobial factors found in human airway surface liquid
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DOI：
10.1152/ajplung.2000.279.5.l799
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发表时间：
2000-11-01
影响因子：
4.9
通讯作者：
Welsh, MJ
中科院分区：
文献类型：
--
作者：
Singh, PK;Tack, BF;Welsh, MJ
气道表面液体含有多种因素，被认为是提供针对气道中沉积的细菌的第一道防线。虽然已经研究了单个因素的抗菌作用，但对它们如何组合工作知之甚少。我们研究了在气道表面液体中发现的六种抗菌肽的联合作用。溶菌酶-乳铁蛋白、溶菌酶分泌性白细胞蛋白酶抑制剂（SLPI）和乳铁蛋白-SLPI的配对组合具有协同作用。溶菌酶、乳铁蛋白和SLPI的三重组合显示出甚至更大的协同作用。其他涉及人β-防御素、LL-37和妥布霉素的组合（通常通过吸入给予囊性纤维化患者）是相加的。由于囊性纤维化患者的气道表面液体盐浓度可能升高，我们检查了盐对协同组合的影响。随着离子强度的增加，协同作用丧失。我们的数据表明，气道表面液体的抗菌效力可能会显着增加抗菌因子之间的协同作用和添加剂的相互作用。这些结果还表明，可能存在于囊性纤维化中的盐浓度增加可能通过减少这些协同相互作用来抑制气道防御。
Airway surface liquid contains multiple factors thought to provide a first line of defense against bacteria deposited in the airways. Although the antimicrobial action of individual factors has been studied, less is known about how they work in combination. We examined the combined action of six antimicrobial peptides found in airway surface liquid. The paired combinations of lysozyme-lactoferrin, lysozyme-secretory leukocyte protease inhibitor (SLPI), and lactoferrin-SLPI were synergistic. The triple combination of lysozyme, lactoferrin, and SLPI showed even greater synergy. Other combinations involving the human beta -defensins, LL-37, and tobramycin (often administered to cystic fibrosis patients by inhalation) were additive. Because the airway surface liquid salt concentration may be elevated in cystic fibrosis patients, we examined the effect of salt on the synergistic combinations. As the ionic strength increased, synergistic interactions were lost. Our data suggest that the antibacterial potency of airway surface liquid may be significantly increased by synergistic and additive interactions between antimicrobial factors. These results also suggest that increased salt concentrations that may exist in cystic fibrosis could inhibit airway defenses by diminishing these synergistic interactions.