Review: Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application

Abstract

Lactoferrin is an iron-binding glycoprotein present in various secretions (eg. milk, tears, saliva,pancreatic juice, etc.). It is also stored in specific granules of polymorphonuclear granulocytes from which it is released following activation. Lactoferrin exerts a bactericidal activity by damaging the outermembrane of Gram-negative bacteria, as well as immunoregulatory functions by decreasing the release of interleukin-l (IL- 1), IL-2 and tumor necrosis factor-alpha INF-alpha) and enhancing monocyte and natural killer cell cytotoxicity. Lactoferrin binds with high affinity to lipid A, the toxic moiety of the lipopolysaccharide, or endotoxin from Gram-negative bacteria Lipopolysacchride interaction with monocytes/ma phages results in the production and release of TNF-alpha, that plays an important role in inducing septic shock In this respect, it has recently been demonstrated that lactoferrin inhibits the lipopolysaccharide interaction with CD14 on monocytes/macrophages by competition with the lipopolysaccharide binding protein. Therefore, besides its bactericidal activity, lactoferrin may also act by neutralizing the toxic effects of lipopolysaccharide and this protective role against endotoxin lethal shock has been demonstrated in animal models. Moreover, in vitro and in vivo neutralization of endotoxin by a human lactoferrin-derived peptide was also reported and lactoferrin or lactoferrin-derived peptides could represent useful tools for the treatment of endotoxin-induced septic hock. The recent production and characterization of monoclonal antibodies against different epitopes of human lactoferrin, including monoclonal antibodies selectively neutralizing lactoferrin binding to lipid A, may allow a better elucidation of the consequence of lactoferrin-lipopolysaccharide interaction.

Histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and alters HagB-induced chemokine responses

“…These include salivary gland derived peptides23, fibronectin24, LL-37252627, lactoferrin2829, human neutrophil peptide (HNP) α defensins3031, and HBDs1622. Therefore, we believe that, histatin 5, in the physiologic range of human saliva, has the ability to significantly attenuate select chemokines and cytokines produced in dendritic cells exposed to HagB, a virulence factor of the periodontal pathogen P. gingivalis .…”

Antimicrobial Peptides: Old Molecules with New Ideas

“…Numbers in parentheses indicate references. (1) , (Ganz et al , 1985; Harder et al , 2001; Johnston et al , 2011); (2) , (Frohm et al , 1997); (3) , (Harder and Schroder, 2002); (4) , (Glaser et al , 2005); (5) , (Cumberbatch et al , 2000); (6) , (Marchini et al , 2002); (7) , (Wingens et al , 1998); (8) , (Meyer-Hoffert et al , 2003); (9) , (Cutuli et al , 2000; Schauer et al , 1994); (10) , (Radek et al , 2008); (11) , (Abtin et al , 2010); (12) , (Cogen et al , 2010b); (13) , (Di Nardo et al , 2003); (14) , (Ganz, 2003); (15) , (Agerberth et al , 1995; Cowland et al , 1995); (16) , (Caccavo et al , 2002); (17) , (Belaaouaj et al , 2000); (18) , (Murakami et al , 2004); (19) , (Schittek et al , 2001); (20) , (Ali et al , 2001; Oono et al , 2006); (21) , (Stenger et al , 1998); (22) , (Chronnell et al , 2001; Nagy et al , 2006; Nakatsuji et al , 2010); (23) , (Lee et al , 2009b); (24) , (Glaser et al , 2005); (25) , (Lee et al , 2008). …”

The Emerging Role of Peptides and Lipids as Antimicrobial Epidermal Barriers and Modulators of Local Inflammation

“…Antimicrobial peptides that have the ability to attenuate the production of chemokines and pro-inflammatory cytokines to microbial antigens include salivary gland derived peptides [97], LL-37 [98-100], lactoferrin [101, 102], HNP α defensins [103-105], and human β defensins [84, 106, 107]. Human neutrophils dying by apoptosis or necrosis release HNPs that inhibit the secretion of multiple pro-inflammatory cytokines from macrophages [105].…”