These data suggest a therapeutic potential for probiotics in the treatment of postmenopausal osteoporosis. Atherosclerosis is a progressive inflammatory condition resulting in cellular changes in the arterial intima with fatty deposits, socalled atheroma. Oxidatively modified low density lipoproteins are involved and are associated with elevated levels of lipoproteins in blood. High cholesterol and fatty diets are priming events. The innate immune system is central to the pathology and plays a role in initiation and progression of the disease. Complement and complement activation are key elements of the innate immune system. There are three pathways by which the C system can be activated: classical pathway, lectin pathway and the alternative pathway. The enzymatic generation of C3a from C3 and subsequently C5a from C5 with relevant receptors leads to complement-mediated chemoattraction of inflammatory cells. In atherosclerotic lesions, the complement anaphylatoxins C3a and C5a bind to receptors expressed by plaque intima macrophages, T cells, mast cells, endothelial and medial smooth muscle cells and therefore have a role in orchestrating the inflammatory component of atherosclerosis. Properdin is the only naturally occurring positive regulator of complement activation, leading to an amplification of ongoing complement activation. Macrophages in the atherosclerotic Reversine plaques may present as lipid laden foam cells and can be of M1 or M2 phenotype. Our recent work has shown that properdindeficient mice in comparison with their littermate wildtype controls exhibit an immune response which is compatible with a bias towards M2 activity. The intact alternative pathway of complement plays a proatherogenic role in response to a high fat diet in mice. No study has yet examined the effect of genetic deletion of properdin on atherosclerosis. Properdin is a non-enzymatic serum glycoprotein and is the only positive regulator of AP. Typically oligomers of properdin interact with Factor B bound C3b to stabilize the alternative C3 and C5 convertases that then cleave more C3 and C5. Our comprehensive study indicates a protective effect of properdin in male mice but only under conditions of ‘mild’ atherosclerosis. We show that as a result of properdin deletion on a hyperlipidemic background, circulating complement C3 accumulates, alternatively activated macrophage infiltration in aortic lesions is enhanced and lesion size is increased. In more advanced disease with significant hypercholesterolemia, this protective effect is overwhelmed by other systems and signalling pathways. C3 behaves as an acute phase reactant similar to CRP and is increased in atherosclerotic lesions. ASP is produced from C3 by adipsin and Factor B. Properdin stabilizes the C3 convertase so in the presence of properdin there should be more ASP and less in its absence. Our data suggest that in all diets and genders of mice, there is a decrease of up to 50% in the ratio of ASP/C3, consistent with less production of ASP.