title: Suppression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with beta 2-glycoprotein I.
abstract: BACKGROUND
  Atherosclerosis is considered analogous to chronic inflammatory diseases. Beta 2-glycoprotein I (beta 2GPI) is a phospholipid binding protein shown to serve as a target for prothrombotic antiphospholipid antibodies. It has recently been demonstrated to drive an immune mediated reaction and enhance murine atherosclerosis. Oral tolerance is a method in which feeding a given antigen, downregulates the respective immune responses towards it, and attenuates concomitant organ specific disorders. Herein, we tested the hypothesis, that inhibiting cellular immunity to beta 2GPI would result in suppression of fatty streak formation in mice.
  
  
  RESULTS
  LDL receptor deficient mice were fed different doses of human or bovine beta 2GPI or BSA and than switched to an atherogenic diet. To determine the effect of feeding on lymph node proliferative indices, separate groups of mice were fed beta 2GPI and then immunized with the respective antigen. Feeding either human or bovine beta 2GPI was effective in attenuating atherosclerosis as compared to control fed animals. Oral feeding with of beta 2GPI inhibited lymph node cell reactivity to beta 2GPI in mice immunized against the human protein. Oral tolerance was also capable of reducing reactivity to oxidized LDL in mice immunized against oxLDL. IL-4 and IL-10 production was upregulated in lymph node cells of beta 2GPI-tolerant mice immunized against beta 2GPI, upon priming with the respective protein.
  
  
  CONCLUSIONS
  Thus, oral administration of beta 2GPI is an effective means of suppressing atherogenesis in mice and should further be investigated.
authors.affiliation: Department of Cardiology, Tel Aviv Medical Center, Israel. jacobg@post.tau.ac.il
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.forename: Niva
authors.initials: N
authors.lastname: Yacov
authors.forename: Eyal
authors.initials: E
authors.lastname: Breitbart
authors.forename: Livnat
authors.initials: L
authors.lastname: Bangio
authors.forename: Aviv
authors.initials: A
authors.lastname: Shaish
authors.forename: Boris
authors.initials: B
authors.lastname: Gilburd
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
authors.forename: Dror
authors.initials: D
authors.lastname: Harats
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D001161:Arteriosclerosis / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage* / Q000276:immunology; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008077:Lipoproteins, LDL / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics*; D053482:beta 2-Glycoprotein I
chemical_list: D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein; D016753:Interleukin-10; D015847:Interleukin-4