关键词: AJ, Adherens junctions ANG-1, Angiopoietin 1 AQP, Aquaporins BBB, blood brain barrier CNS, Central nervous system COPD, Chronic obstructive pulmonary disease EAE, Experimental autoimmune encephalomyelitis EPAC1, Exchange protein activated by cyclic AMP ERK1/2, Extracellular signal-regulated kinases 1 and 2 Endothelial barrier FA, Focal adhesions FAK, focal adhesion tyrosine kinase FoxO1, Forkhead box O1 GAG, Glycosaminoglycans GDNF, Glial cell-derived neurotrophic factor GJ, Gap junctions GPCR, G-protein coupled receptors GTPase, Guanosine 5'-triphosphatase HMGB-1, High mobility group box 1 HRAS, Harvey rat sarcoma viral oncogene homolog ICAM-1, Intercellular adhesion molecule 1 IL-1β, Interleukin 1 beta IP3, Inositol 1,4,5-triphosphate JAM, Junctional adhesion molecules MEK, Mitogen-activated protein kinase kinase MLC, Myosin light chain MLCK, Myosin light-chain kinase MMP, Matrix metalloproteinases NO, Nitric oxide OSM, Oncostatin M PAF, Platelet activating factor PDE, Phosphodiesterase PKA, Protein kinase A PNA, Platelet-neutrophil aggregates ROS, Reactive oxygen species Rac1, Ras-related C3 botulinum toxin substrate 1 Rap1, Ras-related protein 1 RhoA, Ras homolog gene family, member A S1P, Sphingosine-1-phosphate SCID, Severe combined immunodeficient SOCS-3, Suppressors of cytokine signaling 3 Shp-2, Src homology 2 domain-containing phosphatase 2 Src, Sarcoma family of protein kinases TEER, Transendothelial electrical resistance TGF-beta1, Transforming growth factor-beta1 TJ, Tight junctions TNF-, Tumor necrosis factor alpha VCAM-1, Vascular cell adhesion molecule 1 VE, Vascular endothelial VE-PTP, Vascular endothelial receptor protein tyrosine phosphatase VEGF, Vascular endothelial growth factor VVO, Vesiculo-vacuolar organelle ZO, Zonula occludens cAMP, 3'-5'-cyclic adenosine monophosphate erythrocytes leukocytes pSrc, Phosphorylated Src platelets vascular permeability

来  源:   DOI:10.4161/21688370.2014.978720   PDF(Sci-hub)

Abstract:
The barrier properties of endothelial cells are critical for the maintenance of water and protein balance between the intravascular and extravascular compartments. An impairment of endothelial barrier function has been implicated in the genesis and/or progression of a variety of pathological conditions, including pulmonary edema, ischemic stroke, neurodegenerative disorders, angioedema, sepsis and cancer. The altered barrier function in these conditions is often linked to the release of soluble mediators from resident cells (e.g., mast cells, macrophages) and/or recruited blood cells. The interaction of the mediators with receptors expressed on the surface of endothelial cells diminishes barrier function either by altering the expression of adhesive proteins in the inter-endothelial junctions, by altering the organization of the cytoskeleton, or both. Reactive oxygen species (ROS), proteolytic enzymes (e.g., matrix metalloproteinase, elastase), oncostatin M, and VEGF are part of a long list of mediators that have been implicated in endothelial barrier failure. In this review, we address the role of blood borne cells, including, neutrophils, lymphocytes, monocytes, and platelets, in the regulation of endothelial barrier function in health and disease. Attention is also devoted to new targets for therapeutic intervention in disease states with morbidity and mortality related to endothelial barrier dysfunction.
摘要:
内皮细胞的屏障特性对于维持血管内和血管外隔室之间的水和蛋白质平衡至关重要。内皮屏障功能的损害与各种病理状况的发生和/或进展有关。包括肺水肿,缺血性卒中,神经退行性疾病,血管性水肿,败血症和癌症。在这些条件下,屏障功能的改变通常与从常驻细胞中释放可溶性介质有关(例如,肥大细胞,巨噬细胞)和/或募集的血细胞。介体与内皮细胞表面表达的受体的相互作用通过改变内皮间连接中粘附蛋白的表达来降低屏障功能。通过改变细胞骨架的组织,或者两者兼而有之。活性氧(ROS),蛋白水解酶(例如,基质金属蛋白酶,弹性蛋白酶),制瘤素M,和VEGF是涉及内皮屏障衰竭的一长串介质的一部分.在这次审查中,我们讨论了血细胞的作用,包括,中性粒细胞,淋巴细胞,单核细胞,和血小板,在健康和疾病中调节内皮屏障功能。还关注在具有与内皮屏障功能障碍相关的发病率和死亡率的疾病状态中治疗性干预的新靶标。
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