Polysialic acid interacts with lactoferrin and supports its activity to inhibit the release of neutrophil extracellular traps

The Bovine Antimicrobial Peptide Lactoferricin Interacts with Polysialic Acid without Loss of Its Antimicrobial Activity against Escherichia coli

“…Recently, the linear carbohydrate polysialic acid (polySia) has been identified as a probable binding partner for lactoferrin [11,12]. The building units of this polysaccharide are sialic acids, a group of α-keto acids with a nine-carbon backbone [13].…”

“…Thus, LFcin binds polySia without loss of its protective activity as an antimicrobial peptide.Lactoferrin can be excreted by epithelial cells, and the highest amounts have been determined in breast milk [8,9]. Besides epithelial cells, neutrophil granulocytes belong to the major producer of lactoferrin and, thus, high concentrations of lactoferrin can be found at inflammatory hotspots [7,8,10].Recently, the linear carbohydrate polysialic acid (polySia) has been identified as a probable binding partner for lactoferrin [11,12]. The building units of this polysaccharide are sialic acids, a group of α-keto acids with a nine-carbon backbone [13].…”

“…In mammals, however, only α2,8-linked polymers, consisting of N-acetylneuraminic acid (Neu5Ac) residues, seem to be generated, modulating numerous physiological processes, such as the development of the brain and other organs, in addition to immunological mechanisms [13,[15][16][17][18][19][20][21][22]. Interestingly, polySia and lactoferrin can be detected in the same bodily fluids, such as ejaculates, blood, and milk, suggesting that polySia influences the functional properties of lactoferrin [1,12,[23][24][25]. Indeed, polySia has been shown to support the activity of lactoferrin in inhibiting the release of neutrophil extracellular traps (NET) [3,12].…”

“…Interestingly, polySia and lactoferrin can be detected in the same bodily fluids, such as ejaculates, blood, and milk, suggesting that polySia influences the functional properties of lactoferrin [1,12,[23][24][25]. Indeed, polySia has been shown to support the activity of lactoferrin in inhibiting the release of neutrophil extracellular traps (NET) [3,12]. NET is a pathogen-catching meshwork of decondensed DNA and antimicrobial molecules that can be formed by neutrophil granulocytes during inflammation [26], and polySia is only one example of several carbohydrate-based mechanisms that influence the formation and functionality of NET [27].…”

“…The proteolytic release might be an advantage due to the commonly stronger antimicrobial activity of LFcin compared to lactoferrin [5,6,29,[32][33][34]. These antibacterial effects, in addition to the observation that bacteria show increasing resistance against antibiotics, make LFcin an interesting alternative or additional therapeutic agent in veterinary and human medicine [34].It has already been shown that polySia interacts with the LFcin-containing domain in lactoferrin, as well as with the released antimicrobial peptide LFcin [11,12]. Remarkably, polySia also interacts with histones [35,36], which are, like LFcin, denoted as antimicrobial peptides [37][38][39].…”