Id |
Subject |
Object |
Predicate |
Lexical cue |
T31 |
0-23 |
Sentence |
denotes |
Discovery and Structure |
T32 |
24-212 |
Sentence |
denotes |
Human LF is a cationic glycosylated protein consisting of 691 amino acids (9) folded into two globular lobes (80 kDa bi-lobal glycoprotein) (10), that are connected by an α-helix (11, 12). |
T33 |
213-253 |
Sentence |
denotes |
Bovine LF contains 689 amino acids (13). |
T34 |
254-427 |
Sentence |
denotes |
LF was first discovered and isolated from bovine milk in 1939 (14), and is a member of the transferrin family (60% amino acid sequence identity with serum transferrin) (11). |
T35 |
428-652 |
Sentence |
denotes |
LF and transferrin have similar amino acid compositions, secondary structures (including their disulphide linkages), and tertiary structures, although they differ in terms of biological functions (11, 15, 16) (see Figure 2). |
T36 |
653-811 |
Sentence |
denotes |
There are also three different isoforms: LF-α is the iron-binding isoform, while LF- β and LF-g both have ribonuclease activity but do not bind iron (11, 17). |
T37 |
812-906 |
Sentence |
denotes |
When it is iron-rich it is referred to hololactoferrin and when iron-free apolactoferrin (18). |
T38 |
907-1144 |
Sentence |
denotes |
The tertiary structures of the two forms are significantly different: apolactoferrin is characterized by an open conformation of the N-lobe and a closed conformation of the C-lobe, while both lobes are closed in the hololactoferrin (18). |
T39 |
1145-1333 |
Sentence |
denotes |
Human LF and bovine LF possess high sequence homology and have very similar antibacterial, antifungal, antiviral, antiparasitic, anti-inflammatory, and immunomodulatory activities (19–21). |
T40 |
1334-1442 |
Sentence |
denotes |
Consequently, it is common to give the bovine form rather than say a recombinant human form as a supplement. |
T41 |
1443-1614 |
Sentence |
denotes |
Bovine LF is also deemed a “generally recognized as safe” substance by the Food and Drug Administration (FDA, USA), and is commercially available in large quantities (19). |
T42 |
1615-1747 |
Sentence |
denotes |
Figure 2 Crystal structures of bovine lactoferrin (PDB code = 1BLF), human lactoferrin (1B0L), and rabbit serum transferrin (1JNF). |
T43 |
1748-1772 |
Sentence |
denotes |
Adapted from Vogel (10). |
T44 |
1773-1829 |
Sentence |
denotes |
Pink spheres represent ferric iron (Fe3+) binding sites. |
T45 |
1830-2033 |
Sentence |
denotes |
Due to its similarities to transferrin, which is the main iron transporting molecule in serum (22, 23), α-LF possesses iron binding capabilities (24, 25), and it can chelate two ferric irons (Fe3+) (26). |
T46 |
2034-2175 |
Sentence |
denotes |
LF binds one ferric iron atom in each of its two lobes; however, an important attribute is that it does not release its iron, even at pH 3.5. |
T47 |
2176-2299 |
Sentence |
denotes |
This is of importance as this property assures iron sequestration in infected tissues where the pH is commonly acidic (27). |
T48 |
2300-2474 |
Sentence |
denotes |
In the context of its iron-binding capabilities, it means that when it binds ferric and siderophore-bound iron, it limits the availability of essential iron to microbes (27). |
T49 |
2475-2668 |
Sentence |
denotes |
In healthy individuals, iron is largely intracellular and sequestered within ferritin or as a co-factor of cytochromes and FeS proteins, and as haem complexed to hemoglobin within erythrocytes. |
T50 |
2669-2727 |
Sentence |
denotes |
Circulating iron is rapidly bound by transferrin (28, 29). |
T51 |
2728-2880 |
Sentence |
denotes |
When erythrocytes lyse and hemoglobin or haem is released into the circulation, their hemoglobin is captured by haptoglobin, and haem by hemopexin (30). |
T52 |
2881-3067 |
Sentence |
denotes |
Here, circulating serum ferroxidase ceruloplasmin is of importance, as LF can bind to ceruloplasmin, such that a direct transfer of ferric iron between the two proteins is possible (31). |
T53 |
3068-3258 |
Sentence |
denotes |
A direct transfer of ferric iron from ceruloplasmin to lactoferrin prevents both the formation of potentially toxic hydroxyl radicals (32) and the utilization of iron by pathogenic bacteria. |
T54 |
3259-3460 |
Sentence |
denotes |
LF is therefore an important player in preventing bacteria from acquiring and sequestering iron, which [with the possible exception of Borrelia burgdorferi (33)]; they require for growth and virulence. |
T55 |
3461-3575 |
Sentence |
denotes |
LF also acts as biomarker, as it is commonly upregulated when the host is suffering from various kinds of disease. |
T56 |
3576-3612 |
Sentence |
denotes |
See Table 1 for selected references. |
T57 |
3613-3732 |
Sentence |
denotes |
Table 1 Lactoferrin as a major player in host defense and iron binding, and its use as biomarker for various diseases. |
T58 |
3733-3760 |
Sentence |
denotes |
Area of action References |
T59 |
3761-3805 |
Sentence |
denotes |
Protecting neonates via breast milk (34–41) |
T60 |
3806-3924 |
Sentence |
denotes |
LF in cervicovaginal mucosa and female reproductive tract; antibacterial, antifungal antiparasitic, antiviral (42–45) |
T61 |
3925-3952 |
Sentence |
denotes |
LF in the airways (46, 47) |
T62 |
3953-4009 |
Sentence |
denotes |
Mucosal surfaces, allergen-induces skin infections (48) |
T63 |
4010-4062 |
Sentence |
denotes |
Neutrophil extracellular trap (NET) production (49) |
T64 |
4063-4128 |
Sentence |
denotes |
Saliva and its antimicrobial activities and iron binding (50–52) |
T65 |
4129-4183 |
Sentence |
denotes |
Saliva as biomarker for neurological diseases (53–55) |
T66 |
4184-4253 |
Sentence |
denotes |
Saliva as biomarker for periodontal disease and oral dryness (56–59) |