Atherosclerosis 189 (2006) 83–90 Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice Jose R. Faria-Neto 1 , Kuang-Yuh Chyu ∗,1 , Xiaojun Li, Paul C. Dimayuga, Carmel Ferreira, Juliana Yano, Bojan Cercek, Prediman K. Shah Atherosclerosis Research Center, Division of Cardiology, Department of Medicine and Burns and Allen Research Institute, Cedars-Sinai Medical Center and David Geffen School of Medicine at UCLA, Los Angeles, CA 90048, United States Received 13 July 2005; received in revised form 10 November 2005; accepted 20 November 2005 Available online 18 January 2006 Abstract Phosphorylcholine (PC) headgroup is one of the neoantigens exposed by LDL oxidation that can elicit an immune response. Active immunization with Streptococcus pneumoniae, which bears PC on its cell wall, reduced atherosclerosis in hypercholesterolemic mice and this effect was attributed to an immune response to PC. In this study we tested the hypothesis that passive immunization with a monoclonal anti-PC IgM antibody can be athero-protective in a murine model of native aortic and vein graft atherosclerosis. Inferior vena cava from 16-week-old donor male apoE-null mice was grafted into right carotid artery of age-matched male recipient apoE-null mice. Anti-PC IgM titers were evaluated before and 4 weeks after surgery. For the immunization protocol, a separate group of mice received weekly intraperitoneal injection of monoclonal anti-PC IgM (400 g) for 4 weeks, starting the day of surgery. Controls received PBS or pooled polyclonal IgM. Anti-PC IgM titres significantly increased at 4 weeks following surgery. Passive immunization with anti-PC IgM reduced vein graft plaque size and neointimal thickness resulting in a larger luminal area; in addition immunization reduced the inflammatory cell content of the plaques. There was no significant effect on the established native aortic atherosclerotic lesions. Immunization did not affect circulating cholesterol levels. Taken together our data suggest that passive immunization with anti-PC IgM significantly reduces vein graft lesion size with less inflammatory phenotype without affecting cholesterol levels, indicating an athero-protective immune response to PC. Lack of effect on established native aortic lesions may have been due to short duration of therapy and/or reduced efficacy in established lesions as compared to evolving lesions of vein graft atherosclerosis. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Atherosclerosis; Phosphorylcholine; Passive immunization 1. Introduction The role of innate and adaptive immunity in atheroscle- rosis has been increasingly recognized [1–3]. One of the components of innate immune response is natural IgM anti- body [4], which recognizes pathogen-associated molecular patterns (PAMPs) to confer protection against offending ∗ Corresponding author. Tel.: +1 310 423 4876; fax: +1 310 423 0245. E-mail address: Chyuk@cshs.org (K.-Y. Chyu). 1 These authors contributed equally to this manuscript. antigens. A monoclonal anti-phosphorylcholine IgM that bears the TEPC-15 isotype was cloned from a hypercholes- terolemic mouse and found to bind to phosphorylcholine (PC) headgroups on oxidized LDL or phospholipids and block oxLDL uptake by macrophage [5,6]. Phosphorylcholine is the head group of many phospho- lipids and is also an immunodeterminant in the cell wall of Streptococcus pneumoniae. While active immunization with S. pneumoniae expands T15-IgM secreting splenocytes and appears to be associated with reduced atherosclerotic lesion formation [7], it is not clear that the effect is directly 0021-9150/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2005.11.033