Lactoferrin, a bird's eye view

摘要

Lactoferrin is an abundant iron-binding protein in milk. This 80 kDa bilobal glycoprotein is also present in several other secreted bodily fluids, as well as in the secondary granules of neutrophils. The potent iron-binding properties of lactoferrin can locally create iron deficiency, and this is an important factor in host defense as it prevents bacteria from growing and forming biofilms. In addition to having antibacterial activity, lactoferrin is now known to have a long list of other beneficial biological properties. It has direct antiviral, antifungal, and even some anticancer activities. It can also promote wound healing and bone growth, or it can act as an iron carrier. Moreover, lactoferrin displays a cytokine-like "alarmin" activity, and it activates the immune system. Simultaneously, it can bind endotoxin (lipopolysaccharide), and in doing so, it modulates the activity of the host immune response. The majority of these intriguing biological activities reside in the unique positively charged N-terminal region of the protein. Interestingly, several peptides, which retain many of the beneficial activities, can be released from this region of lactoferrin. An isoform of the human protein, known as delta-lactoferrin, is expressed inside many cells, where it acts as a transcription factor. Lactoferrin purified from human and bovine milk have very similar but not completely identical properties. Lactoferrin receptors have been identified on the surface of various cells, and some of these can bind both the human and the bovine protein. Because of the extensive health-promoting effects of lactoferrin, there has been considerable interest in the use of bovine or human lactoferrin as a "protein nutraceutical" or as a therapeutic protein. When lactoferrin is used as a "biologic drug", it seems to be orally active in contrast to most other therapeutic proteins.