Adhesion and signaling by B cell-derived exosomes: the role of integrins
Adhesion and signaling by B cell-derived exosomes: the role of integrins
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DOI：
10.1096/fj.03-1094fje
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发表时间：
2004-04-01
期刊：
影响因子：
4.8
通讯作者：
Hallett, MB
中科院分区：
文献类型：
--
作者：
Clayton, A;Turkes, A;Hallett, MB
外泌体是由各种细胞分泌的纳米大小的囊泡，在生理上具有潜在的不同作用。虽然强调它们参与免疫调节，但尚未认识到它们具有更广泛的生物效应的潜力。外泌体的一个共同特征是粘附分子的表达，其中包括整合素家族。我们首次通过检测外泌体（固定在小珠上）与细胞外基质（ECM）成分和细胞因子处理的成纤维细胞的粘附相互作用，探讨了B细胞来源的外泌体整合素的可能功能。Western blotting和流式细胞术检测整合素（beta1和beta2）的表达。结合研究（与阻断抗体）证明了它们在粘附胶原- 1，纤维连接蛋白和肿瘤坏死因子(TNF)- α活化的成纤维细胞中的功能。通过单细胞成像测量，外泌体粘附到tnf - α活化的成纤维细胞上也引发了细胞质钙的整合素依赖性变化。因此，B细胞衍生的外泌体表达功能性整合素，能够介导对ECM和细胞表面粘附分子的锚定，并且可能是炎症期间在细胞-细胞直接接触之外的距离传递粘附信号的新模式。
Exosomes are nanometer-sized vesicles secreted by various cells, with potentially diverse roles in physiology. Although emphasis has been placed on their involvement in immune modulation, their potential for more wide-ranging biological effects has not been appreciated. A common exosome feature is the expression of adhesion molecules, which include the integrin family. We have for the first time addressed the possible function of B cell-derived exosome-integrins by examining adhesive interactions of exosomes ( immobilized onto beads) with extracellular matrix (ECM) components and cytokine-treated fibroblasts. Integrin (beta1 and beta2) expression was demonstrated by Western blotting and flow cytometry. Binding studies ( with blocking antibodies) demonstrated their function in adhesion to collagen-I, fibronectin, and tumor necrosis factor (TNF)-alpha-activated fibroblasts. Exosome adhesion to TNF-alpha-activated fibroblasts also triggered integrin-dependent changes in cytosolic calcium, measured by single cell imaging. Thus, B cell-derived exosomes express functional integrins, which are capable of mediating anchorage to ECM and cell-surface adhesion molecules, and may be a novel mode of delivering adhesion signals at distances beyond that of direct cell-cell contact during inflammation.