Letter abstract
Nature Medicine 13, 719 - 724 (2007)
Published online: 3 June 2007 | doi:10.1038/nm1601
Mast cells promote atherosclerosis by releasing proinflammatory cytokines
Jiusong Sun1,4, Galina K Sukhova1,4, Paul J Wolters2,4, Min Yang1,3,4, Shiro Kitamoto1, Peter Libby1, Lindsey A MacFarlane1, Jon Mallen-St Clair2 & Guo-Ping Shi1
Mast cells contribute importantly to allergic and innate immune responses by releasing various preformed and newly synthesized mediators1, 2. Previous studies have shown mast cell accumulation in human atherosclerotic lesions3. This report establishes the direct participation of mast cells in atherogenesis in low-density lipoprotein receptor–deficient (Ldlr-/-) mice4. Atheromata from compound mutant Ldlr-/-KitW-sh/W-sh mice5 showed decreased lesion size, lipid deposition, T-cell and macrophage numbers, cell proliferation and apoptosis, but increased collagen content and fibrous cap development. In vivo, adoptive transfer of syngeneic wild-type or tumor necrosis factor (TNF)-
-deficient mast cells restored atherogenesis to Ldlr-/-KitW-sh/W-sh mice. Notably, neither interleukin (IL)-6- nor interferon (IFN)-
-deficient mast cells did so, indicating that the inhibition of atherogenesis in Ldlr-/-KitW-sh/W-sh mice resulted from the absence of mast cells and mast cell–derived IL-6 and IFN-. Compared with wild-type or TNF--deficient mast cells, those lacking IL-6 or IFN- did not induce expression of proatherogenic cysteine proteinase cathepsins from vascular cells in vitro or affect cathepsin and matrix metalloproteinase activities in atherosclerotic lesions, implying that mast cell–derived IL-6 and IFN- promote atherogenesis by augmenting the expression of matrix-degrading proteases. These observations establish direct participation of mast cells and mast cell–derived IL-6 and IFN- in mouse atherogenesis and provide new mechanistic insight into the pathogenesis of this common disease.
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cardiovascular Medicine NRB-7, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
- Department of Medicine, University of California, HSE-201, 513 Parnassus Avenue, San Francisco, California 94143, USA.
- Department of Rheumatology, Nanfang Hospital and Nanfang Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
- These authors contributed equally to this study.
Correspondence to: Guo-Ping Shi1 e-mail: gshi@rics.bwh.harvard.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Mast cells promote atherosclerosis by releasing proinflammatory cytokinesNature Medicine Letter
Mast cell production of IL-4 and TNF may be required for protective and pathological responses in gastrointestinal helminth infectionMucosal Immunology Article Response
Mast cell production of IL-4 and TNF may be required for protective and pathological responses in gastrointestinal helminth infectionMucosal Immunology Article Response
Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumorsNature Medicine Article (01 Oct 2007)
See all 17 matches for Research