[The role of lactoferrin in the iron metabolism. Part II. Antimicrobial and antiinflammatory effect of lactoferrin by chelation of iron].

Lactoferrin (LF) is a glycoprotein widely distributed in mammalian organisms. It is synthesized by epithelial cells; hence it is present in secretions of mucous membranes. It is also contained in secondary granules of neutrophils and released to the circulation during trauma, infection or inflammation. LF belongs to the transferrin family--proteins binding iron ions with a high affinity. Upon isolation in 1961 LF was initially called a red, iron-binding protein. LF's ability to bind iron is associated with other functions which the protein fulfils in the body. As described in the part I. of the article, LF participates in acquisition of iron from food and its storage in the body, and to a certain degree also in iron transport to cells. In this part of the article the effect of LF in combating microorganisms by chelating iron is described. The iron-chelating property of LF renders iron inaccessible to the pathogens, thus restricting their growth. Iron, due to its participation in many metabolic processes, is an essential element for almost all microorganisms. Iron is not easily accessible for pathogens within the host. Since iron is crucial for normal function of both pathogens and the host, an ability to acquire iron during infection is regarded as an important virulence factor. Higher vertebrates have evolved a complicated protection system of iron storage and LF is an important element of this system. Low iron-saturated LF effectively combats bacteria and fungi, acting in a bacteriostatic and fungistatic way. The degree of iron saturation also influences antiviral activity of LF. Some pathogens (e.g. Helicobacter pylori, Neisseria sp, Haemophilus influenzae) have evolved a system of siderophores or cellular receptors which can acquire iron from LF and transferrin. The so-called lactoferrin theory of hypoferremia in inflammation assumes, in addition, a protective role of the protein in inflammation, sepsis and trauma. LF, by chelation and storage of plasma iron in the liver and spleen, temporarily restricts its accessibility for microorganisms and processes of formation of toxic, reactive oxygen species, which contributes to the amelioration of inflammatory states.