Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores
Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores
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DOI：
10.1128/aac.48.9.3367-3372.2004
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发表时间：
2004-09-01
影响因子：
4.9
通讯作者：
Redl, B
中科院分区：
文献类型：
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作者：
Fluckinger, M;Haas, H;Redl, B
人泪液脂质运载蛋白（TL;也称为Lcn 1）是一种分泌蛋白，大量存在于覆盖上皮表面的液体如泪液和呼吸道分泌物中。它被认为是疏水性的，潜在有害分子的生理清道夫，但有证据表明它也抑制细菌生长。在本研究中，我们重新考虑了TL可能通过清除铁载体干扰微生物生长的可能性，如人中性粒细胞明胶酶相关脂质运载蛋白（NGAL）所述。事实上，我们的实验表明，TL结合微生物铁载体具有高亲和力。与NGAL相反，NGAL显示出对细菌儿茶酸盐型铁载体具有一定的特异性，TL结合广泛的铁载体，包括细菌儿茶酸盐型肠杆菌素和异羟肟酸盐型去铁胺B，以及所有主要类别的真菌铁载体。在铁限制条件下，添加外源TL可以抑制细菌和真菌的生长。因此，TL可能是先天免疫系统的一个新成员，特别是参与粘膜防御真菌感染。
Human tear lipocalin (TL; also known as Lcn1) is a secretory protein present in large amounts in fluids that cover epithelial surfaces such as tears and respiratory secretions. It is supposed to act as a physiological scavenger of hydrophobic, potentially harmful molecules, but there is evidence that it also inhibits bacterial growth. In the present study, we reconsidered the possibility that TL might interfere with microbial growth by scavenging of siderophores, as described for human neutrophil gelatinase-associated lipocalin (NGAL). Indeed, our experiments revealed that TL binds to microbial siderophores with high affinities. In contrast to NGAL, which was shown to have some specificity for bacterial catecholate-type siderophores, TL binds to a broad array of siderophores, including bacterial catecholate-type enterobactin and hydroxamate-type desferrioxamine B, and all major classes of fungal siderophores. By adding exogenous TL, bacterial and fungal growth could be inhibited under iron-limiting conditions. Thus, TL might be a novel member of the innate immune system especially involved in mucosal defense against fungal infections.