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Lactadherin (also known as milk fat globule factor 8, MFG-F8) is a 47 kDa glycoprotein that was found in milk fat globule membranes. Lactadherin is secreted into milk by mammary epithelial cells of humans, cows and mice. Its presence in milk is associated with protecting a breast-fed children against rotavirus infections. The protein is also produced by vascular smooth muscle cells, endothelial cells and macrophages. Lactadherin at the N-terminal part has an EGF-like domain (epidermal growth factor-like domain) enabling its binding to aVb5 and aVb3 integrins and at the C-terminus has a C2 domain responsible for a stereospecific binding to phosphatidyl-L-serine (PS). The presence of such structures determines multiple physiological functions of this protein. Lactadherin secreted by macrophages promotes the phagocytosis of apoptotic particles by forming a bridges between PS on apoptotic cells and aVb3 integrins on phagocytes. Lactadherin deficiency leads to accumulation of apoptotic cell debris in subendo- thelium and thus alters the protective immunologic response which leads to an acceleration of atherosclerotic plaque development. Lactadherin may also play a role in the clearance of PS-expressing platelet derived microparticles from the circulation thus reducing hypercoagulable state. PS binding C2 domain of lactadherin shares homology with the C2 domains of blood coagulation factor VIII and factor V. Due to its relatively low molecular weight and resistance to digest lactadherin may serve as an easy bioavailable molecule with high potency to inhibit (competitively) factors VIII and V binding with PS-expressing platelets, platelet derived microparticles or erythrocytes and thus reduce formation of procoagulant tenase and prothrombinase complexes. Lactadherin exhibits a great similarity to annexin V. However, in contrast to annexin V, lactadherin binds to the membranes at much lower PS concentration and in the absence of calcium. This review presents evidence supporting these novel roles of lactadherin.
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The Editorial Board
Andrzej Łukaszyk - przewodniczący, Zofia Bielańska-Osuchowska, Szczepan Biliński, Mieczysław Chorąży, Aleksander Koj, Włodzimierz Korochoda, Leszek Kuźnicki, Aleksandra Stojałowska, Lech Wojtczak

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