生物谷報道：肥大細胞可以通過釋放多種合成的調節(jié)物參與過敏性和先天性免疫應答,。早先的研究發(fā)現(xiàn)，肥大細胞會在動脈粥樣硬化患者的損傷區(qū)域聚集,，但是它是如何參與作用的并不清楚。最近,，發(fā)表在最新一期《自然－醫(yī)學》雜志上的一篇中國科研人員的文章報道了在低密度脂蛋白缺失的老鼠模型中,，肥大細胞參與動脈粥樣硬化形成的機制。
研究人員發(fā)現(xiàn),，在低密度脂蛋白缺失的老鼠模型中,，產生的動脈粥樣硬化病損傷區(qū)域縮小，脂質沉積減少,，T細胞和巨噬細胞的數(shù)目減少,，同時細胞增殖和編程性死亡的數(shù)目也減少，與之相反的是膠原含量和纖維性蛋白增多,。隨之研究人員在動物體內實驗中發(fā)現(xiàn),，將野生型或腫瘤壞死因子 (TNF- )缺失的肥大細胞轉入該老鼠模型體內，可導致老鼠重新形成動脈粥樣硬化,。但是將白介素-6(IL-6)缺失或 -干擾素 (IFN- )缺失的肥大細胞轉入老鼠模型中不會形成動脈粥樣硬化,。這一結果說明了肥大細胞分泌的白介素-6(IL-6)和 -干擾素 (IFN- )在動脈粥樣硬化形成過程中具有重要的作用此外，研究人員發(fā)現(xiàn),，在注射了白介素-6(IL-6)缺失或 -干擾素 (IFN- )缺失的肥大細胞的老鼠中,，無論是半胱氨酸蛋白酶還是組織蛋白酶和基質金屬蛋白酶的表達都沒有受到影響，這說明了肥大細胞分泌的白介素-6(IL-6)和 -干擾素 (IFN- )是通過增加基質降解的蛋白酶來促進動脈粥樣硬化形成的,。
這一發(fā)現(xiàn)揭示了肥大細胞促進動脈粥樣硬化形成的直接作用機制,，從而為更好地研究這一疾病的發(fā)病機理提供了新的見解。
Figure 1 - Mast cell accumulation in mouse atherosclerotic lesions.
(a) mMCP-4-positive mast cells were localized in the intima and adventitia of an atherosclerotic lesion from an Ldlr-/- mice fed a Western diet for 26 weeks. Boxes, intimal and adventitial immunopositive mast cells. (b,c) The same antibody did not detect mMCP-4-positive mast cells in normal vessels from an Ldlr-/- mouse consuming a chow diet (b) or in an atherosclerotic lesion from an Ldlr-/-KitW-sh/W-sh mouse consuming a Western diet (c). (d) mMCP-4 immunoblot analysis detected a 29-kDa mMCP-4 protein in Hpvtg mouse ear tissue extracts, but not in BMMC or vascular endothelial cells (EC), SMC or macrophages. (e–g) mMCP-4 immunostaining specificity was confirmed by preimmune IgG staining (e) and staining adjacent tissue sections with toluidine blue (f) and mMCP-4 antibody (g) using frozen sections from Ldlr-/- mouse lesions. Insets (f,g), magnified views of degranulated mast cells. Vertical lines, tunica media thickness. Scale bars in a–c,e, 100 m; in f,g, 30 m; in a,f,g insets, 10 m; in b inset, 50 m. Images shown in this figure are representative of 10 (a) or 5 (b,c,e–g) aortic arch sections.
原文出處：
Nature Medicine 13, 719 - 724 (2007)
Published online: 3 June 2007 | doi:10.1038/nm1601
Mast cells promote atherosclerosis by releasing proinflammatory cytokines - pp719 - 724
Jiusong Sun, Galina K Sukhova, Paul J Wolters, Min Yang, Shiro Kitamoto, Peter Libby, Lindsey A MacFarlane, Jon Mallen-St Clair & Guo-Ping Shi
doi:10.1038/nm1601
First paragraph | Full Text | PDF (361 KB) | Supplementary information
相關基因：
IL6
Official Symbol IL6 and Name: interleukin 6 (interferon, beta 2) [Homo sapiens]
Other Aliases: BSF2, HGF, HSF, IFNB2, IL-6
Chromosome: 7; Location: 7p21
Annotation: Chromosome 7, NC_000007.12 (22733344..22738140)
MIM: 147620
GeneID: 3569
Il6
Official Symbol Il6 and Name: interleukin 6 [Mus musculus]
Other Aliases: Il-6
Chromosome: 5; Location: 5 17.0 cM
Annotation: Chromosome 5, NC_000071.5 (30339700..30346507)
GeneID: 16193
IFNA1
Official Symbol IFNA1 and Name: interferon, alpha 1 [Homo sapiens]
Other Aliases: IFL, IFN, IFN-ALPHA, IFNA13, IFNA@, MGC138207, MGC138505, MGC138507
Other Designations: IFN-alpha 1b; OTTHUMP00000045110; interferon alpha 1b
Chromosome: 9; Location: 9p22
Annotation: Chromosome 9, NC_000009.10 (21430439..21431314)
MIM: 147660
GeneID: 3439
