Disorder in Milk Proteins: Lactadherin Multifunctionality and Structure

Abstract

Milk fat globule membrane (MFGM) is one of the milk components that is produced by the lactating mammary glands and released to the milk in the form of vesicles. MFGM surrounds milk fat globule secreted by the milk producing cells and has a complex structure containing various lipids (e.g., triacylglycerides, phospholipids, and cholesterol), proteins and other macromolecules. Among the proteinaceous components of MFGM is lactadherin, also known as milk fat globule-EGF factor 8 protein (MFG-E8). Being one of the main proteins present in MFGM, lactadherin is related to milk secretion, has antimicrobial and antiviral effects, and plays important roles in the immune defense as one of the immune system molecules. Furthermore, lactadherin belongs to the family of secreted extracellular matrix proteins, and clearly can be considered as a multifunctional (or moonlighting) glycoprotein involved in regulation of many biological and physiological processes, such as angiogenesis, atherosclerosis, haemostasis, phagocytosis, and tissue remodeling. This review focuses on the similarities and differences of lactadherin among different species and describes the main functions of this protein, as well as its structure.

Recombinant human milk fat globule-EGF factor VIII (rhMFG-E8) as a therapy for sepsis after acute exposure to alcohol

“…We have previously shown that polymicrobial sepsis after acute alcohol exposure is associated with reduced expression of MFG-E8, and can be ameliorated by the administration of rmMFG-E8 (Wu et al 2010), thus revealing a novel potential targeted therapy for sepsis in alcohol abusers. MFG-E8 is a secreted glycoprotein ubiquitously expressed and abundant in milk, including human breast milk (Yasueda et al 2015; Sabha et al 2018). Mainly produced by phagocytes such as macrophages and dendritic cells, MFG-E8 is necessary for their optimal clearance of dying (mostly apoptotic, but also autophagic, necrotic, necroptotic, pyroptotic) cells (Hanayama et al 2002; Aziz et al 2011).…”

“…Milk fat globule-epidermal growth factor-factor VIII (MFG-E8), also called lactadherin, is a secreted glycoprotein abundant in milk, including human breast milk (Yasueda et al 2015; Sabha et al 2018). We have shown that, among other functions such as anti-coagulant (Shah et al 2012), anti-atherogenic (Miksa et al 2009b), pro-extracellular matrix remodeling (Aziz et al 2013) and enterotrophic activity (Bhatty et al 2017), MFG-E8 has anti-inflammatory properties (Miksa et al 2009a).…”

“…Unlike its mouse orthologue, human MFG-E8 is a 387-amino acid 45-KDa protein with only one N-terminal EGF-like domain and no proline/threonine rich domain (Fig. 1), with an amino acid homology of 63% with mouse MFG-E8 (Sabha et al 2018; Oshima et al 2014).

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More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects

“…It decreases over time during lactation when the child is developing its immune system (L€ onnerdal 2016). Lactadherin, another glycoprotein found in human milk, known as milk fat globule-epidermal growth factor 8 (MFG-E8) as well, has been shown to have specific anti-viral functions and prevents rotaviral infection in the newborn (Sabha et al 2018). More than that, it prevents intestinal inflammation by enhancing the phagocytosis of apoptotic cells (Aziz et al 2017).…”

“…More than that, it prevents intestinal inflammation by enhancing the phagocytosis of apoptotic cells (Aziz et al 2017). In addition, a recent study showed that lactadherin can prevent necrotizing enterocolitis (NEC) by enhancing intestinal barrier integrity (Sabha et al 2018). Milk fat globules (MFGs) are milk lipids present in the form of dispersed droplets (Martini, Salari, and Altomonte 2016).…”