Nguyen L L, D'Amore P A
Schepens Eye Research Institute and Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Int Rev Cytol. 2001;204:1-48. doi: 10.1016/s0074-7696(01)04002-5.
In nature, mammalian cells do not exist in isolation, but rather are involved in interactions with other cells and matrix. In this review, several aspects of cellular interactions that are important in vascular growth and development will be highlighted. The cardiovascular system is the earliest to develop in the embryo. A number of growth factors and their receptors mediate the complex stages of migration, assembly, organization, and stabilization of developing vessels. In the adult organism, normal angiogenesis is restricted primarily to tissue growth (such as muscle and fat), the wound healing process and the female reproductive system. However, pathological angiogenesis, such as with tumor growth, diabetic retinopathy, and arthritis, is of great concern. The identification and/or development of exogenous and endogenous angiogenesis inhibitors has added to the understanding of these pathological processes. In addition to cellular interactions via ligands and receptors, cells also interact directly through physical contacts. These interactions facilitate anchorage, communication, and permeability. Since vessels serve as non-leaky conduits for blood flow as well as interfaces for molecular diffusion, the physical interactions between the cells that make up vessels must be specific for the function at hand. Permeability is a specialized function of vessels and is mediated by intracellular mechanisms and intercellular interactions. Cells also interact with the surrounding extracellular matrix. Integrin-matrix interaction is a two-way exchange critical for angiogenesis. Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases play major roles in embryonic remodeling, adult injury, and pathological conditions. Several experimental model systems have been useful in our understanding of cellular interactions. These in vitro models incorporate heterotypic cell-cell interactions and/or allow cell-matrix interactions to occur.
在自然界中,哺乳动物细胞并非孤立存在,而是参与与其他细胞和基质的相互作用。在本综述中,将重点介绍在血管生长和发育中重要的细胞相互作用的几个方面。心血管系统是胚胎中最早发育的系统。许多生长因子及其受体介导发育中血管迁移、组装、组织和稳定的复杂阶段。在成年生物体中,正常血管生成主要限于组织生长(如肌肉和脂肪)、伤口愈合过程和女性生殖系统。然而,病理性血管生成,如肿瘤生长、糖尿病视网膜病变和关节炎,备受关注。外源性和内源性血管生成抑制剂的鉴定和/或开发增进了对这些病理过程的理解。除了通过配体和受体进行细胞间相互作用外,细胞还通过物理接触直接相互作用。这些相互作用促进锚定、通讯和通透性。由于血管既是血流的无渗漏管道,又是分子扩散的界面,构成血管的细胞之间的物理相互作用必须针对手头的功能具有特异性。通透性是血管的一种特殊功能,由细胞内机制和细胞间相互作用介导。细胞还与周围的细胞外基质相互作用。整合素-基质相互作用是血管生成至关重要的双向交换。基质金属蛋白酶和基质金属蛋白酶组织抑制剂在胚胎重塑、成人损伤和病理状况中起主要作用。几种实验模型系统对我们理解细胞间相互作用很有帮助。这些体外模型纳入了异型细胞间相互作用和/或允许细胞-基质相互作用发生。