Department of Life Sciences, University of Trieste, via Valerio 28, 34127 Trieste, Italy.
Immunol Lett. 2011 Oct 30;140(1-2):7-13. doi: 10.1016/j.imlet.2011.06.006. Epub 2011 Jul 6.
The endothelium is a continuous physical barrier that regulates coagulation and selective passage of soluble molecules and circulating cells through the vessel wall into the tissue. Due to its anatomic localization, the endothelium may establish contact with components of the complement, the kinin and the coagulation systems which are the main, though not exclusive, inducers of vascular leakage. Although the complement and the kinin systems may act independently, increasing evidence suggest that there is a crosstalk that involve different components of both systems. Activation is required for the function of the two systems which are involved in pathological conditions such as hereditary and acquired angioedema (AE) and vasculitidis. The aim of this review is to discuss the contribution of complement and kinin systems to vascular leakage and the cross-talk between the two systems in the development of AE. This clinical condition is characterized by episodic and recurrent local edema of subcutaneous and submucosal tissues and is due to inherited or acquired C1-INH deficiency. Although the pathogenesis of the swelling in patients with AE was originally thought to be mediated by C2, ample evidence indicate bradykinin (BK) as the most effective mediator even though the possibility that both the complement and the kinin-forming systems may contribute to the edema has not been completely excluded. BK induces endothelial leakage interacting with B2 receptors but other molecules may be involved in the onset and maintenance of AE. In this review we shall discuss the role of B1 receptors and gC1qR/p33 in addition to that of B2 receptors in the onset of AE attacks and the importance of these receptors as new possible molecular targets for therapy.
内皮细胞是一种连续的物理屏障，可调节凝血和可溶性分子及循环细胞通过血管壁选择性地进入组织。由于其解剖位置，内皮细胞可能与补体、激肽和凝血系统的成分接触，这些成分是血管渗漏的主要（尽管不是唯一）诱导物。虽然补体和激肽系统可以独立作用，但越来越多的证据表明，这两个系统之间存在涉及不同成分的串扰。两种系统的激活是其发挥功能所必需的，它们参与遗传性和获得性血管性水肿（AE）和血管炎等病理状况。本综述的目的是讨论补体和激肽系统对血管渗漏的贡献，以及这两个系统在 AE 发病机制中的相互作用。这种临床病症的特征是皮下和黏膜下组织的局部间歇性和复发性水肿，是由于遗传或获得性 C1-INH 缺乏引起的。尽管最初认为 AE 患者的肿胀是由 C2 介导的，但大量证据表明缓激肽（BK）是最有效的介质，尽管补体和激肽形成系统都可能导致水肿的可能性尚未完全排除。BK 通过与 B2 受体相互作用诱导内皮细胞渗漏，但其他分子可能参与 AE 的发作和维持。在本综述中，我们将讨论 B1 受体和 gC1qR/p33 的作用，除了 B2 受体在 AE 发作中的作用，以及这些受体作为新的可能的治疗分子靶点的重要性。
