MCP-1, a highly expressed chemokine in dengue haemorrhagic fever/dengue shock syndrome patients, may cause permeability change, possibly through reduced tight junctions of vascular endothelium cells

Abstract

Vascular leakage, one hallmark of dengue haemorrhagic fever (DHF) and dengue shock syndrome, has been linked to the mediators secreted from cells in the circulatory system. In this study, extremely high expression levels of monocyte chemoattractant protein-1 (MCP-1) were found in the plasma of DHF patients compared with low MCP-1 expression levels in the plasma of enterovirus 71-infected patients. It was also found that MCP-1 expression was induced in dengue virus 2 (DV2)-infected monocytes and lymphocytes, but not in liver or endothelial cells. Exposing monolayers of human umbilical vein endothelial cells (HUVECs) to recombinant human MCP-1 (rhMCP-1) or to the culture supernatant of DV2-infected human monocytes increased the vascular permeability of the cells. MCP-1-neutralizing monoclonal antibody only partially prevented monolayer permeability change. Consistently, the distribution of the tight junction protein ZO-1 on the cellular membranes of HUVECs was disrupted by rhMCP-1 or by the conditioned medium of DV2-infected monocytes. In summary, it was found that the increased permeability and disrupted tight junctions of human vascular endothelium cells were effected through a mechanism partially dependent on MCP-1, which was secreted by DV2-infected monocytes and lymphocytes.

Spectrum of disease outcomes in mice infected with YFV-17D

“…In humans, severe DENV, YFV and YFV-17D-associated viscerotropic disease are potentially mediated by dysregulated secretion of cytokines and chemokines (Bae et al, 2008;Lee et al, 2006b;Monath, 2008;ter Meulen et al, 2004). We found significantly elevated serum levels of IP-10 and MCP-1 in mice with viscerotropic disease as compared with mice with neurotropic disease and mice displaying no clinical signs of disease (Fig.…”

“…MCP-1 levels were elevated in DENV-infected humans (Lee et al, 2006a;Rathakrishnan et al, 2012), severe YFV and YFV-17D infections in humans (Bae et al, 2008;ter Meulen et al, 2004), YFV-infected IFN-a/b and IFN-a/b/c receptor knockout mice (Meier et al, 2009;Thibodeaux et al, 2012), and in some strains of WNV-infected mice (Kumar et al, 2013). MCP-1 has previously been shown to increase vascular permeability and disrupt tight junctions in endothelial cells, suggesting a potential role in haemorrhagic manifestations and shock syndrome characteristic of fatal YFV and DENV infections (Lee et al, 2006b;Rathakrishnan et al, 2012).…”

Elevated levels of soluble ST2 protein in dengue virus infected patients

“…Cross reactivity also generates a dysfunctional T cell response that results in suboptimal clearance of the virus and an uncontrolled production of soluble mediators [9]. Elevated circulating levels of both type 1 (Th1) and type 2 (Th2) cytokines and various chemokines including gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1beta (IL-1β), IL-6, IL-10, IL-13, IL-8, macrophage chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein 1 beta (MIP-1β) have been detected in dengue infected patients [10][11][12][13][14][15][16][17][18], and the kinetics and persistence of some of these mediators seem to be related to the severity of the disease.…”

Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles

“…4C, D), although with borderline significance (0.0624 < p < 0.0782; in a Wilcoxon test). RANTES and MCP-1 are both chemokines related to severity of infection (Lee et al 2006, Pulendran et al 2008) and were only slightly increased after infection (Fig. 4E, F).…”

“…Chemokines also have an important role in pathogenesis. For example, IP-10/CXCL-10 was found to be elevated in dengue haemorrhagic fever (DHF) (Fink et al 2007) and MCP-1/CCL-2 ( Lee et al 2006), while MIP-1β/CCL-4 is associated with a good prognosis (Bozza et al 2008). Elevated serum levels of IL-6, IL-8, TNF-α, MCP-1, IL-1 receptor agonist (Ra) and IL-10 were observed in fatal YF cases when compared with non-fatal cases (Bae et al 2008).…”