Lactadherin orthologs inhibit migration of human, porcine and murine intestinal epithelial cells.

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.