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Tissue Barriers. 2015 Apr 3;3(1-2):e978720. doi: 10.4161/21688370.2014.978720. eCollection 2015.

Blood cells and endothelial barrier function.

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Department of Clinical and Toxicological Analyses; School of Pharmaceutical Sciences; University of Sao Paulo ; Sao Paulo, Brazil.
Department of Molecular and Cellular Physiology; Louisiana State University Health Sciences Center ; Shreveport, LA USA.


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.


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

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