乳铁蛋白(Lactoferrin, Lf)是分子量大小约为80 kDa的铁离子结合糖蛋白,是转铁蛋白(Transferrin, Tf)家族的成员之一。其理化性质独特,具有抑菌、抗病毒、抗癌、免疫调节、调节铁离子的吸收等诸多生物学功能。获得高产且有生物活性的重组乳铁蛋白,并用于临床治疗,一直是研究热点。随着基因工程技术的发展,已获得多个可表达重组乳铁蛋白的表达系统。本文对乳铁蛋白的理化性质、生物学活性、临床研究以及目前的重组表达系统进行综述,以期为乳铁蛋白的临床应用提供参考。
Lactoferrin is an iron-binding glycoprotein with a molecular weight of about 80 kDa that belongs to the transferrin family. Due to its unique physical and chemical properties, lactoferrin has a variety of biological functions including antibacterial, antiviral, anticancer, immunomodulatory activities and regulation of iron absorption. High-yield production of recombinant lactoferrin with biological activity and its application in clinical treatment have been a hot topic for long time. With the development of genetic engineering techniques, various expression systems have been developed to produce recombinant lactoferrin. In this review, we summarize physicochemical characteristics, biological activities, clinical studies and current recombinant expression systems of lactoferrin, in order to provide references for its clinical application.
[1] Vorland LH. Lactoferrin: a multifunctional glycoprotein. APMIS , 1999, 107(7-12): 971-981.
[2] Johanson B. Isolation of an iron-containing red protein from human milk. Acta Chem Scandinav , 1960, 14(2): 510-512.
[3] Lönnerdal B, Iyer S. Lactoferrin: molecular structure and biological function. Annu Rev Nutr , 1995, 15(1): 93-110.
[4] García-Montoya IA, Cendón TS, Arévalo-Gallegos S, Rascón-Cruz Q. Lactoferrin a multiple bioactive protein: an overview. Biochim Biophys Acta , 2012, 1820(3): 226-236.
[5] Chen K, Zhang L, Li H, Zhang Y, Xie H, Shang J, Tian WZ, Yang P, Chai LY, Mao M. Iron metabolism in infants: influence of bovine lactoferrin from iron-fortified formula. Nutrition , 2015, 31(2): 304-309.
[6] Valenti P, Berlutti F, Conte MP, Longhi C, Seganti L. Lactoferrin functions: current status and perspectives. J Clin Gastroenterol , 2004, 38(Suppl. 6): S127-S129.
[7] Wakabayashi H, Oda H, Yamauchi K, Abe F. Lactoferrin for prevention of common viral infections. J Infect Chemother , 2014, 20(11): 666-671.
[8] van der Strate BW, Beljaars L, Molema G, Harmsen MC, Meijer DK. Antiviral activities of lactoferrin. Antiviral Res , 2001, 52(3): 225-239.
[9] Zhang YL, Lima CF, Rodrigues LR. In vitro evaluation of bovine lactoferrin potential as an anticancer agent. Int Dairy J , 2015, 40: 6-15.
[10] de la Rosa G, Yang D, Tewary P, Varadhachary A, Oppenheim JJ. Lactoferrin acts as an alarmin to promote the recruitment and activation of APCs and antigen-specific immune responses. J Immunol , 2008, 180(10): 6868-6876.
[11] Kruzel ML, Actor JK, Zimecki M, Wise J, Ploszaj P, Mirza S, Kruzel M, Hwang SA, Ba X, Boldogh I. Novel recombinant human lactoferrin: differential activation of oxidative stress related gene expression. J Biotechnol , 2013, 168(4): 666-675.
[12] Blais A, Fan CB, Voisin T, Aattouri N, Dubarry M, Blachier F, Tomé D. Effects of lactoferrin on intestinal epithelial cell growth and differentiation: an in vivo and in vitro study. Biometals , 2014, 27(5): 857-874.
[13] Umuhumuza LC, Niu WM, Sun XL. Effect of bovine lactoferrin and casein peptide powder on microbial growth and glucose utilization by microorganisms in pork meat during storage at 4ºC. Pakistan J Nutrit , 2011, 10(3): 208-213.
[14] Tamura Y. Production and application of bovine lactoferrin. Bull-Int Dairy Federat , 2004, (389): 64-68.
[15] Balcão VM, Costa CI, Matos CM, Moutinho CG, Amorim M, Pintado ME, Gomes AP, Vila MM, Teixeira JA. Nanoencapsulation of bovine lactoferrin for food and biopharmaceutical applications. Food Hydrocolloids , 2013, 32(2): 425-431.
[16] Metz-Boutigue MH, Jollès J, Mazurier J, Schoentgen F, Legrand D, Spik G, Montreuil J, Jollès P. Human lactotransferrin: amino acid sequence and structural comparisons with other transferrins. Eur J Biochem , 1984, 145(3): 659-676.
[17] Bezault J, Bhimani R, Wiprovnick J, Furmanski P. Human lactoferrin inhibits growth of solid tumors and development of experimental metastases in mice. Cancer Res , 1994, 54(9): 2310-2312.
[18] Byrne SL, Krishnamurthy D, Wessling-Resnick M. Pharmacology of iron transport. Annu Rev Pharmacol Toxicol , 2013, 53: 17-36.
[19] Weinberg ED. Human lactoferrin: a novel therapeutic with broad spectrum potential. J Pharm Pharmacol , 2001, 53(10): 1303-1310.
[20] Lambert LA, Perri H, Halbrooks PJ, Mason AB. Evolution of the transferrin family: conservation of residues associated with iron and anion binding. Comp Biochem Physiol B Biochem Mol Biol , 2005, 142(2): 129-141.
[21] Sharma S, Sinha M, Kaushik S, Kaur P, Singh TP. C-lobe of lactoferrin: the whole story of the half-molecule. Biochem Res Int , 2013, 2013: Article ID 271641.
[22] Wang JR, Tian ZG, Teng D, Yang YL, Hu JC, Wang JH. Cloning, expression and characterization of Kunming mice lactoferrin and its N-lobe. Biometa
