Ellison R T
Department of Medicine, University of Massachusetts School of Medicine, Worcester 01655, USA.
Adv Exp Med Biol. 1994;357:71-90. doi: 10.1007/978-1-4615-2548-6_8.
Lactoferrin is an iron-binding protein found in human mucosal secretions as well as the specific granules of polymorphonuclear leukocytes. A variety of functions have been ascribed to the protein, and it appears to contribute to antimicrobial host defense. In particular, it has been shown to have direct effects on pathogenic microorganisms including bacteriostasis and the induction of microbial iron uptake systems. Still its overall physiologic role remains to be defined. It has appeared logical that antimicrobial activity of the protein arises from sequestration of environmental iron thereby causing nutritional deprivation in susceptible organisms. This argument is buttressed by the finding that selected highly virulent pathogens have evolved techniques to subvert this effect and use the protein as an iron source. However, recent observations indicate that the protein has additional properties that contribute to host defense. Work by several groups has shown that the protein synergistically interacts with immunoglobins, complement, and neutrophil cationic proteins against Gram-negative bacteria. Further, both the whole protein and a cationic N-terminus peptide fragment directly damage the outer membrane of Gram-negative bacteria suggesting a mechanism for the supplemental effects. This review will summarize these diverse observations with a consideration of how the in vitro work relates to the physiological role of the protein.
乳铁蛋白是一种存在于人体黏膜分泌物以及多形核白细胞的特定颗粒中的铁结合蛋白。该蛋白具有多种功能，似乎有助于宿主的抗菌防御。特别是，已证明它对包括抑菌作用和诱导微生物铁摄取系统在内的病原微生物有直接影响。但其整体生理作用仍有待确定。蛋白质的抗菌活性源于对环境中铁的螯合，从而导致易感生物体内营养缺乏，这似乎是合乎逻辑的。这一观点得到了以下发现的支持：某些高毒力病原体已经进化出颠覆这种作用的技术，并将该蛋白用作铁源。然而，最近的观察表明，该蛋白具有有助于宿主防御的其他特性。几个研究小组的工作表明，该蛋白与免疫球蛋白、补体和中性粒细胞阳离子蛋白协同作用对抗革兰氏阴性菌。此外，完整蛋白和阳离子N端肽片段都会直接损伤革兰氏阴性菌的外膜，这表明了其产生补充作用的机制。本综述将总结这些不同的观察结果，并考虑体外研究与该蛋白生理作用之间的关系。
