Enjeti Anoop K, Lincz Lisa F, Seldon Michael
Department of Haematology level 4, Hunter Haematology Research Group, New Medical Building, Calvary Mater Hospital, Waratah Newcastle, Australia.
Semin Thromb Hemost. 2008 Oct;34(7):683-91. doi: 10.1055/s-0028-1104547. Epub 2008 Dec 15.
Microparticles (MPs) are small fragments of membrane-bound cytoplasm that are shed from the surface of an activated or apoptotic cell. Recently, their function as vectors of transcellular exchange of biologic information, in addition to better described forms of intercellular communication such as growth factors, cytokines, and chemokines, has become well recognized. Circulating levels of MPs are thought to reflect a balance between cell stimulation, proliferation, and death. The production of MPs is thought to predominately occur by vesiculation or blebbing of the cell membrane. The mechanisms governing the remodeling of the plasma membrane are complex, involving cytoskeletal changes and a shift from normal phospholipid asymmetry. Increased intracellular calcium subsequent to cell activation leads to intracellular increases in several proteins including gelsolin and calpain, as well as the activity of enzymes such as translocase, floppase, and scramblase, which play important roles in the homeostasis of the cell membrane. The membrane vesiculation and phospholipids asymmetry leading to the production of MPs occurs by the complex interplay of the proteins involved. There are several clinical conditions associated with elevated MPs, and most are also associated with an increased risk of thrombosis. Apart from cardiovascular disease and venous thromboembolism, MPs are also elevated in solid tumors with metastatic disease. The measurement of MPs is being regarded as a potential biomarker, given the range of conditions in which they are elevated and the association with prothrombotic states. The utility of measuring MPs as a diagnostic and prognostic marker is currently a subject of intense investigation. The further development of the various methods for the detection and measurement of MPs and prospective clinical trials establishing the utility of such tests will be critical prior to the routine measurement of MPs in the diagnostic laboratory.
微粒(MPs)是从活化或凋亡细胞表面脱落的膜结合细胞质小片段。最近,它们作为生物信息跨细胞交换载体的功能,除了诸如生长因子、细胞因子和趋化因子等已被更好描述的细胞间通讯形式外,已得到广泛认可。MPs的循环水平被认为反映了细胞刺激、增殖和死亡之间的平衡。MPs的产生被认为主要通过细胞膜的囊泡化或出泡作用发生。控制质膜重塑的机制很复杂,涉及细胞骨架变化以及从正常磷脂不对称性的转变。细胞活化后细胞内钙的增加导致包括凝溶胶蛋白和钙蛋白酶在内的几种蛋白质在细胞内增加,以及诸如转位酶、翻转酶和翻转酶等酶的活性增加,这些酶在细胞膜的稳态中起重要作用。导致MPs产生的膜囊泡化和磷脂不对称性是由相关蛋白质的复杂相互作用引起的。有几种临床情况与MPs升高有关,而且大多数情况也与血栓形成风险增加有关。除了心血管疾病和静脉血栓栓塞外,MPs在伴有转移疾病的实体瘤中也会升高。鉴于MPs升高的多种情况以及与血栓前状态的关联,MPs的测量被视为一种潜在的生物标志物。将MPs作为诊断和预后标志物进行测量的效用目前是深入研究的课题。在诊断实验室常规测量MPs之前,进一步开发各种检测和测量MPs的方法以及开展确定此类检测效用的前瞻性临床试验至关重要。