Macrophage-specific expression of mannose-binding lectin controls atherosclerosis in low-density lipoprotein receptor-deficient mice.
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.
Matthijsen
Robert A
RA
Department of Surgery, Maastricht University Medical Centre and School for Nutrition and Metabolism, Maastricht, Netherlands.
de Winther
Menno P J
MP
Kuipers
Dian
D
van der Made
Ingeborg
I
Weber
Christian
C
Herias
M Veronica
MV
Gijbels
Marion J J
MJ
Buurman
Wim A
WA
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*
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; C445639:Mbl2 protein, mouse; D011973:Receptors, LDL; C069858:mannose binding protein A; D002784:Cholesterol; D008049:Lipase