title: Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency.
abstract: BACKGROUND
  Deficiency of secreted IgM (sIgM-/-) accelerates atherosclerosis in Ldlr-/-mice. Several atheroprotective effects of increased levels of IgM antibodies have been suggested, including preventing inflammation induced by oxidized low-density lipoprotein and promoting apoptotic cell clearance. However, the mechanisms by which the lack of sIgM promotes lesion formation remain unknown.
  
  
  OBJECTIVE
  To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice.
  
  
  RESULTS
  We here show that both sIgM-/-and Ldlr-/-sIgM-/-mice develop increased plasma IgE titers because of impaired generation of B cells expressing the low-affinity IgE receptor CD23, which mediates the clearance of IgE antibodies. We further report that Ldlr-/-sIgM-/-mice exhibit increased numbers of activated mast cells and neutrophils in the perivascular area of atherosclerotic plaques. Treatment with an anti-IgE-neutralizing antibody fully reversed vascular inflammation and accelerated atherosclerotic lesion formation in cholesterol-fed Ldlr-/-sIgM-/-mice.
  
  
  CONCLUSIONS
  Thus, our data identify a previously unsuspected mechanism by which sIgM deficiency aggravates atherosclerosis.
authors.affiliation: From the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (D.T., M.O.-K., L.G., K.H., C.J.B.); Department of Laboratory Medicine, Medical University of Vienna, Austria (D.T., M.O.-K., L.G., T.P., K.H., C.J.B.); Division of Biopharmaceutics, LACDR Leiden University, The Netherlands (I.B., J.K.); Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond (D.H.C.); and Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (Z.M.).
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsiantoulas
authors.affiliation: From the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (D.T., M.O.-K., L.G., K.H., C.J.B.); Department of Laboratory Medicine, Medical University of Vienna, Austria (D.T., M.O.-K., L.G., T.P., K.H., C.J.B.); Division of Biopharmaceutics, LACDR Leiden University, The Netherlands (I.B., J.K.); Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond (D.H.C.); and Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (Z.M.).
authors.forename: Ilze
authors.initials: I
authors.lastname: Bot
authors.affiliation: From the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (D.T., M.O.-K., L.G., K.H., C.J.B.); Department of Laboratory Medicine, Medical University of Vienna, Austria (D.T., M.O.-K., L.G., T.P., K.H., C.J.B.); Division of Biopharmaceutics, LACDR Leiden University, The Netherlands (I.B., J.K.); Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond (D.H.C.); and Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (Z.M.).
authors.forename: Maria
authors.initials: M
authors.lastname: Ozsvar-Kozma
authors.affiliation: From the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (D.T., M.O.-K., L.G., K.H., C.J.B.); Department of Laboratory Medicine, Medical University of Vienna, Austria (D.T., M.O.-K., L.G., T.P., K.H., C.J.B.); Division of Biopharmaceutics, LACDR Leiden University, The Netherlands (I.B., J.K.); Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond (D.H.C.); and Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (Z.M.).
authors.forename: Laura
authors.initials: L
authors.lastname: Göderle
authors.affiliation: From the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (D.T., M.O.-K., L.G., K.H., C.J.B.); Department of Laboratory Medicine, Medical University of Vienna, Austria (D.T., M.O.-K., L.G., T.P., K.H., C.J.B.); Division of Biopharmaceutics, LACDR Leiden University, The Netherlands (I.B., J.K.); Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond (D.H.C.); and Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (Z.M.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Perkmann
authors.affiliation: From the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (D.T., M.O.-K., L.G., K.H., C.J.B.); Department of Laboratory Medicine, Medical University of Vienna, Austria (D.T., M.O.-K., L.G., T.P., K.H., C.J.B.); Division of Biopharmaceutics, LACDR Leiden University, The Netherlands (I.B., J.K.); Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond (D.H.C.); and Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (Z.M.).
authors.forename: Karsten
authors.initials: K
authors.lastname: Hartvigsen
authors.affiliation: From the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (D.T., M.O.-K., L.G., K.H., C.J.B.); Department of Laboratory Medicine, Medical University of Vienna, Austria (D.T., M.O.-K., L.G., T.P., K.H., C.J.B.); Division of Biopharmaceutics, LACDR Leiden University, The Netherlands (I.B., J.K.); Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond (D.H.C.); and Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (Z.M.).
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Conrad
authors.affiliation: From the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (D.T., M.O.-K., L.G., K.H., C.J.B.); Department of Laboratory Medicine, Medical University of Vienna, Austria (D.T., M.O.-K., L.G., T.P., K.H., C.J.B.); Division of Biopharmaceutics, LACDR Leiden University, The Netherlands (I.B., J.K.); Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond (D.H.C.); and Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (Z.M.).
authors.forename: Johan
authors.initials: J
authors.lastname: Kuiper
authors.affiliation: From the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (D.T., M.O.-K., L.G., K.H., C.J.B.); Department of Laboratory Medicine, Medical University of Vienna, Austria (D.T., M.O.-K., L.G., T.P., K.H., C.J.B.); Division of Biopharmaceutics, LACDR Leiden University, The Netherlands (I.B., J.K.); Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond (D.H.C.); and Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (Z.M.).
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.affiliation: From the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (D.T., M.O.-K., L.G., K.H., C.J.B.); Department of Laboratory Medicine, Medical University of Vienna, Austria (D.T., M.O.-K., L.G., T.P., K.H., C.J.B.); Division of Biopharmaceutics, LACDR Leiden University, The Netherlands (I.B., J.K.); Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond (D.H.C.); and Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (Z.M.). christoph.binder@meduniwien.ac.at dimitris.tsiantoulas@meduniwien.ac.at.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood*; D007075:Immunoglobulin M / Q000172:deficiency*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D015415:Biomarkers; D007075:Immunoglobulin M; C033027:secretory IgM; D007073:Immunoglobulin E
keywords: B-lymphocytes; arteriosclerosis; atherosclerosis; immune system; immunoglobulin E; immunoglobulin M; inflammation