Development of inflammatory angiogenesis by local stimulation of Fas in vivo
Development of inflammatory angiogenesis by local stimulation of Fas in vivo
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DOI：
10.1084/jem.186.1.147
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发表时间：
1997-07-07
影响因子：
15.3
通讯作者：
Camussi, G
中科院分区：
文献类型：
--
作者：
Biancone, L;DeMartino, A;Camussi, G
Fas-Fas配体相互作用被认为是通过诱导淋巴细胞凋亡来控制淋巴细胞增殖的重要机制。然而，Fas也广泛表达于非淋巴细胞，其在体内的功能仍有待确定。在这项研究中，我们描述了激动性抗Fas单克隆抗体乔2诱导的小鼠模型中，基质胶是作为一种媒介物用于交付介质的炎症性血管生成的发展。含有mAb Jo 2的Matrigel小鼠皮下植入物迅速被内皮细胞和分散的单核细胞和巨噬细胞浸润。新血管形成和开通后，观察到中性粒细胞明显的血管内积聚和外渗。在炎性浸润中也检测到几个肥大细胞。这种现象与剂量和时间有关，需要肝素的存在。通过观察到炎性血管生成仅限于激动性抗Fas mAb，并且在lpr Fas突变小鼠中不存在，表明对Fas活化的依赖性。在植入物内部或周围组织中的任何时间均未检测到凋亡细胞，这表明血管浸润不是由凋亡细胞募集吞噬细胞引起的，而是由通过Fas接合的刺激信号引起的。这些发现表明Fas-Fas配体相互作用在促进局部血管生成和炎症中的作用。
Fas-Fas ligand interaction is thought to be a crucial mechanism in controlling lymphocyte expansion by inducing lymphocyte apoptosis. However, Fas is also broadly expressed on nonlymphoid cells, where its function in vivo remains to be determined. In this study, we describe the development of inflammatory angiogenesis induced by agonistic anti-Fas mAb Jo2 in a murine model where Matrigel is used as a vehicle for the delivery of mediators. The subcutaneous implants in mice of Matrigel containing mAb Jo2 became rapidly infiltrated by endothelial cells and by scattered monocytes and macrophages. After formation and canalization of new vessels, marked intravascular accumulation and extravasation of neutrophils were observed. Several mast cells were also detected in the inflammatory infiltrate. The phenomenon was dose and time dependent and required the presence of heparin. The dependency on activation of Fas is suggested by the observation that the inflammatory angiogenesis was restricted to the agonistic anti-Fas mAb and it was absent in lpr Fas-mutant mice. Apoptotic cells were not detectable at any time inside the implant or in the surrounding tissue, suggesting that angio infiltration did not result from recruitment of phagocytes by apoptotic cells but rather by a stimulatory signal through Fas-engagement. These findings suggest a role for Fas-Fas ligand interaction in promoting local angiogenesis and inflammation.