title: Macrophage-specific expression of mannose-binding lectin controls atherosclerosis in low-density lipoprotein receptor-deficient mice.
abstract: BACKGROUND
  With consideration of the central role of the innate immune system in atherogenesis and mannose-binding lectin (MBL) as an innate regulator of immunity, the role of MBL in experimental and human atherosclerosis was assessed.
  
  
  RESULTS
  With the use of immunohistochemistry and polymerase chain reaction, deposition and gene expression of MBL-A and -C were assessed in murine atherosclerosis from mice deficient for the low-density lipoprotein receptor (LDLR(-/-)) after 10 or 18 weeks of high-fat feeding. MBL was present and was produced in 10-week-old lesions, whereas deposition and gene expression were minimal after 18 weeks of high-fat feeding and absent in healthy vasculature. Interestingly, deposition of MBL-A and -C differed: MBL-A predominantly localized in upper medial layers, whereas MBL-C was found in and around intimal macrophages. To further study the role of local MBL production by monocytic cells in atherosclerosis, LDLR(-/-) mice with MBL-A and -C(-/-) monocytic cells were construed by bone marrow transplantation. Mice carrying MBL-A and -C double deficient macrophages had increased (30%) atherosclerotic lesions compared with wild-type controls (P=0.015) after 10 weeks of high-fat diet. Subsequently, analysis of MBL deposition and gene expression in advanced human atherosclerotic lesions revealed the presence of MBL protein in ruptured but not stable atherosclerotic lesions. Putatively in agreement with murine data, no MBL gene expression could be detected in advanced human atherosclerotic lesions.
  
  
  CONCLUSIONS
  These results are the first to show that MBL is abundantly present and locally produced during early atherogenesis. Local MBL expression, by myeloid cells, is shown to critically control development of atherosclerotic lesions.
authors.affiliation: Department of Surgery, Maastricht University Medical Centre and School for Nutrition and Metabolism, Maastricht, Netherlands.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Matthijsen
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
authors.forename: Dian
authors.initials: D
authors.lastname: Kuipers
authors.forename: Ingeborg
authors.initials: I
authors.lastname: van der Made
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: M Veronica
authors.initials: MV
authors.lastname: Herias
authors.forename: Marion J J
authors.initials: MJ
authors.lastname: Gijbels
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D008049:Lipase / Q000097:blood; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; C445639:Mbl2 protein, mouse; D011973:Receptors, LDL; C069858:mannose binding protein A; D002784:Cholesterol; D008049:Lipase