Serum from dengue virus-infected patients with and without plasma leakage differentially affects endothelial cells barrier function in vitro

• Published in: PloS one Vol. 12; no. 6; p. e0178820
• Main Authors: Tramontini Gomes de Sousa Cardozo, Francielle, Baimukanova, Gyulnar, Lanteri, Marion Christine, Keating, Sheila Marie, Moraes Ferreira, Frederico, Heitman, John, Pannuti, Cláudio Sérgio, Pati, Shibani, Romano, Camila Malta, Cerdeira Sabino, Ester
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.06.2017; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Biology and Life Sciences; Blood & organ donations; Blood Donors; Blood Platelets; Care and treatment; Chemokines; Chemokines - blood; Child; Child, Preschool; Colony-stimulating factor; Correlation; Cytokines; Cytokines - blood; Dengue; Dengue - blood; Dengue - pathology; Dengue - virology; Dengue fever; Dengue hemorrhagic fever; Dengue virus; Dengue Virus - metabolism; Dengue Virus - pathogenicity; Detection; Diagnostic systems; Disease control; Disruption; Dosage and administration; Electrical resistance; Endothelial cells; Endothelial Cells - pathology; Endothelial Cells - virology; Endothelium; Eotaxin; Granulocyte-macrophage colony-stimulating factor; Health aspects; Homeostasis; Hospitals; Human Umbilical Vein Endothelial Cells; Humans; Immune response; Immune system; Impedance; In vitro methods and tests; Incubation; Infant; Infant, Newborn; Infections; Interleukin 1; Interleukin 10; Interleukin 6; Interleukin 8; IP-10 protein; Laboratories; Leakage; Medicine; Medicine and Health Sciences; Middle Aged; Monitoring; Parasitic diseases; Pathogenesis; Patients; Permeability; Plasma; Platelets; Prevention; Proteins; Serum Albumin - metabolism; Serum levels; Umbilical vein; Vector-borne diseases; Viral diseases; Viral Load; Viruses; Warning; Brazil; United States > US; San Francisco California; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0178820

Although most of cases of dengue infections are asymptomatic or mild symptomatic some individuals present warning signs progressing to severe dengue in which plasma leakage is a hallmark. The present study used Electric Cell-substrate Impedance Sensing (ECIS®) which allows for electrical monitoring of cellular barrier function measuring changes in Transendothelial Electric Resistance (TEER) to investigate the parameters associated with dengue induced leakage. Three groups of individuals were tested: dengue-positives with plasma leakage (leakage), dengue-positives without plasma leakage (no leakage), and dengue-negatives (control). Data show that TEER values of human umbilical vein endothelial cells (HUVECs) was significantly lower after incubation with serum from subjects of the leakage group in comparison to the no leakage or control groups. The serum levels of CXCL1, EGF, eotaxin, IFN-γ, sCD40L, and platelets were significantly decreased in the leakage group, while IL-10, IL-6, and IP-10 levels were significantly increased. We also found a strong correlation between TEER values and augmented levels of IP-10, GM-CSF, IL-1α, and IL-8, as well as decreased levels of CXCL1 and platelets. The present work shows that the magnitude of the immune response contributes to the adverse plasma leakage outcomes in patients and that serum components are important mediators of changes in endothelial homeostasis during dengue infections. In particular, the increased levels of IP-10 and the decreased levels of CXCL1 and platelets seem to play a significant role in the disruption of vascular endothelium associated with leakage outcomes after DENV infection. These findings may have important implications for both diagnostic and therapeutic approaches to predict and mitigate vascular permeabilization in those experiencing the most severe clinical disease outcomes after dengue infection.