Abstract
Lactadherin was originally described due to its appearance in milk, but is abundantly expressed especially by professional and nonprofessional phagocytes. The proteins has been shown to have a multitude of bioactive effects, including inhibition of inflammatory phospholipases, induction of effero‐ and phagocytosis, prevent rotavirus induced gastroenteritis, and modulate intestinal homeostasis by regulating epithelial cell migration. The level of expression seems to be important in a row of serious pathologies linked to the intestinal epithelial barrier function, vascular‐ and autoimmune disease. This study examines the ability of lactadherin to modulate migration of intestinal epithelium. A cell exclusion assay is used to quantify the ability of human, bovine and murine lactadherin orthologs to affect migration of primary small intestine epithelium cells. Previous reports show that recombinant murine lactadherin stimulate rat small intestine cell migration. The present study could not confirm this. Conversely, 10 μg/ml lactadherin inhibits migration. Therefore, as lactadherins enteroprotective properties is well established using in vivo models we conclude that the protective effects are linked to lactadherins ability operate as an opsonin, or other modulating effects, and not a direct lactadherin‐cell induction of migration. Thus, the molecular mechanism behind the enteroprotective role of lactadherin remains to be established.
Highlights
Lactadherin, called milk fat globule epidermal growth factor 8 (MFG-E8), is a 409 amino acid glycoprotein which has been increasingly investigated and found to play multiple roles in diverse cellular interactions important in both normal biology and states of disease, for example, macrophage phagocytosis, inflammation, adult onset- autoimmune lupus-like pathology, splenomegaly, and defective germinal center formation (for review see (Raymond, Ensslin, & Shur, 2009; Aziz, Jacob, Matsuda, & Wang, 2011))
Bovine lactadherin comprises two N-terminal epidermal growth factor homology domains and the C-terminal region consists of two C domains (C1 and C2), which share homology with the lipid-binding “C” domains of blood coagulation factor VIII and factor V
It was hypothesized that lactadherin by the two-sided binding affinities could operate as an opsonin facilitating PS-dependent phagocytosis of apoptotic cells (Andersen, Graversen, Fedosov, & Petersen, 2000) which was consecutively confirmed in vivo (Hanayama, Tanaka, Miwa, & Shinohara, 2002)
Summary
Lactadherin, called milk fat globule epidermal growth factor 8 (MFG-E8), is a 409 amino acid glycoprotein which has been increasingly investigated and found to play multiple roles in diverse cellular interactions important in both normal biology and states of disease, for example, macrophage phagocytosis, inflammation, adult onset- autoimmune lupus-like pathology, splenomegaly, and defective germinal center formation (for review see (Raymond, Ensslin, & Shur, 2009; Aziz, Jacob, Matsuda, & Wang, 2011)). It was suggested that lactadherin has the ability to influence intestinal maintenance and repair in inflammatory bowel models by inducing the migration rate of rat small intestine cells (Bu, Zuo, Wang, & Ensslin, 2007). This effect was efficacious from as little as 2 nmol/L recombinant murine lactadherin (long isoform) and a three-fold increase in migration was observed at 10 n mol/L. In contradiction with previous reports, none of the lactadherin orthologs induced statistically significant migration on any of the enterocyte cell lines tested
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
