生物谷报道：肥大细胞可以通过释放多种合成的调节物参与过敏性和先天性免疫应答。早先的研究发现，肥大细胞会在动脉粥样硬化患者的损伤区域聚集，但是它是如何参与作用的并不清楚。最近，发表在最新一期《自然－医学》杂志上的一篇中国科研人员的文章报道了在低密度脂蛋白缺失的老鼠模型中，肥大细胞参与动脉粥样硬化形成的机制。
研究人员发现，在低密度脂蛋白缺失的老鼠模型中，产生的动脉粥样硬化病损伤区域缩小，脂质沉积减少，T细胞和巨噬细胞的数目减少，同时细胞增殖和编程性死亡的数目也减少，与之相反的是胶原含量和纤维性蛋白增多。随之研究人员在动物体内实验中发现，将野生型或肿瘤坏死因子 (TNF- )缺失的肥大细胞转入该老鼠模型体内，可导致老鼠重新形成动脉粥样硬化。但是将白介素-6(IL-6)缺失或 -干扰素 (IFN- )缺失的肥大细胞转入老鼠模型中不会形成动脉粥样硬化。这一结果说明了肥大细胞分泌的白介素-6(IL-6)和 -干扰素 (IFN- )在动脉粥样硬化形成过程中具有重要的作用此外，研究人员发现，在注射了白介素-6(IL-6)缺失或 -干扰素 (IFN- )缺失的肥大细胞的老鼠中，无论是半胱氨酸蛋白酶还是组织蛋白酶和基质金属蛋白酶的表达都没有受到影响，这说明了肥大细胞分泌的白介素-6(IL-6)和 -干扰素 (IFN- )是通过增加基质降解的蛋白酶来促进动脉粥样硬化形成的。
这一发现揭示了肥大细胞促进动脉粥样硬化形成的直接作用机制，从而为更好地研究这一疾病的发病机理提供了新的见解。
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.
原文出处：
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
相关基因：
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
