MFG-E8: Origin, Structure, Expression, Functions and Regulation

Abstract

Milk Fat Globule-Epidermal Growth Factor-Factor 8 (MFG-E8) with bivalent binding activity to integrin receptors and acidic phospholipids is a secretary glycoprotein exhibiting versatile functions in cell physiology affecting health and diseases. Recent progress in genomics and structural biology studies, in addition to long time accumulation of classical biochemical studies, has been showing its unique molecular structure advantageous to the link between cells and their target cells as well as molecular complexes and its critical roles in regulating inflammation and immunity. MFG-E8 is expressed and secreted by a variety of cells and tissues, especially professional and non-professional phagocytes such as macrophages, immature dendritic cells and the epithelial cells of mammary glands and epididymis. Although MFG-E8 expression has been shown to be up-regulated by a lactogenic hormone, prolactin (PRL), and neuronal chemokine, fractalkine, molecular mechanisms involved in MFG-E8 expression in health and disease states remain largely unknown. The secreted MFG-E8 specifically recognizes the acidic phospholipids and opsonized the targets to be cleared by phagocytosis mainly in paracrine and occasionally in endocrine manners. In addition to the enhancing role in phagocytosis, MFG-E8 binds to its target cells expressing MFG-E8 receptors and acts as a ligand, which modulates inflammatory responses. Moreover, MFG-E8 alone shows ligand activity to intestinal epithelial cells locally exposing the acidic phospholipids and vascular endothelial cells expressing the integrins.