Exosomes: The Messengers of Health and Disease

摘要

Cell to cell communication is an essential process in multicellular organisms. Methods of cellular communications are evolutionarily conserved processes. They involve signaling molecules being released into the extracellular space and interacting with membrane receptors on the surfaces of the recipient cell [1]. Cells are also able to directly interact by exchanging macromolecules through either gap junctions or tunneling nanotubes, making electrical and metabolic synchronizing among groups of cells possible [2, 3]. One of the most fascinating methods of cell-to-cell communications is by way of vesicles formed from membrane structures and released into the extracellular space [4]; these vesicles are called exosomes.HistoryExosomes were first described by Stahl and Johnstone in the 1980s. They were described as nano-sized vesicles discovered during reticulocyte maturation [5, 6]. It was hypothesized that these vesicles functioned to eliminate unwanted cellular proteins from the cytoplasm of the cell [7]. They were further classified as a way to eliminate unnecessary components, more specifically, receptors, from the plasma membrane during reticulocyte maturation. Within the last few years, the complexity of exosome functions began to unravel and appreciate including immune response induction [5, 8-10] plus many additional other functions [4, 11, 12].The importance of intercellular communication by way of exosomes was evident by the evolutionary conserved process in the formation of these vesicles. Exosomes have been shown to be involved in the cellular communication across many different types of living organisms: from prokaryotes to eukaryotes. These vesicles are secreted by protists [13, 14], fungi [15], plants [16], invertebrate [17-19] and vertebrate animals [12].Exosomes have been shown to be both produced and released by many different healthy cell types, including epithelial cells [20-30], adipocytes and fibroblasts [31], nervous system cells including Schwann cells [31], astrocytes [20, 32] and neurons [20, 32]. They were first detected to secrete by hematopoietic cells, more specifically reticulocytes [20, 33, 34], subsequently other hematopoietic cells including B lymphocytes, T cells [10, 20, 21, 35-37], platelets [20, 21, 35-39], mast cells [10, 20, 21, 35-38, 40], dendritic cells [10, 20, 35, 36, 38], and macrophages [40, 41]. In addition, these nanovesicles are present in many different types of biological fluids, such as blood, breast milk, urine, sperm, amniotic fluid, saliva, bronchoalveolar lavage, cerebrospinal fluid, synovial fluid, pleura effusions, and ascites [8, 31, 42, 43].Exosomes are among multiple types of vesicles within a cell, including microvesicles, apoptotic bodies, etc., all of which vary by the size and characteristic proteins they contain and the method of biogenesis. The discrimination between the vesicle types is typically based on size; Apoptotic bodies are in the 50-500nm diameter range and microvesicles are in the 100-1000nm range [11]. For exosomes, various sizes were reported in the literature ranging from 10-140nm [5, 11, 36]. Other distinct characteristics of exosomes are their lipid bilayer structure and density (1.13-1.21 g/ml flotation on a sucrose gradient) [44], which is utilized in the specific isolation of these vesicles from cell culture media and biological fluids. There is a division between two different types of exosomes; one is involved in the presentation of antigens and are immunologically active, and the second group is involved in the communication between cells specifically utilizing RNA [45].