Antibodies against dengue virus nonstructural protein-1 induce heme oxygenase-1 via a redox-dependent pathway in human endothelial cells

Immenschuh, Stephan; Rahayu, Puji; Bayat, Behnat; Saragih, Hendry; Rachman, Andhika

doi:10.1016/j.freeradbiomed.2012.10.551

Cited by 11 publications

(9 citation statements)

References 42 publications

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“…19,32 Recently, our group has shown an important role for ROS in inducing endothelial dysfunction after antibody binding (anti-non-structural glycoprotein-1). 33 More recently, Strait et al 34 have given preliminary evidence that non-bone marrow-derived cells, most likely the pulmonary vascular endothelium, seem to play a crucial role in TRALI induced by antibodies against major histocompatibility complex (MHC) class I. Taking advantage of the cross-reactivity between human anti-HNA-3a antibodies and murine CTL2, we were able to demonstrate that (1) antibody binding to pulmonary vascular endothelium can directly affect barrier integrity leading to lung edema; (2) these effects are not Fc dependent; (3) production of ROS in the endothelium is a critical event in this pathway by inducing VE-cadherin removal from the endothelial junction; and (4) neutrophils seem not to be an initiator in anti-HNA-3a-mediated TRALI; however, their presence may aggravate the destructive effects of anti-HNA-3a.…”

Section: Discussionmentioning

confidence: 99%

Anti–Human Neutrophil Antigen-3a Induced Transfusion-Related Acute Lung Injury in Mice by Direct Disturbance of Lung Endothelial Cells

Bayat

Tjahjono

Sydykov

et al. 2013

ATVB

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Objective— Antibodies against human neutrophil antigen-3a (HNA-3a) located on choline transporter-like protein 2 induce severe transfusion-related acute lung injury (TRALI). This study aims to identify the mechanism implicated in anti–HNA-3a-mediated TRALI. Approach and Results— Our analysis shows that anti–HNA-3a recognizes 2 choline transporter-like protein 2 isoforms (P1 and P2) on human microvascular endothelial cells from lung blood vessels but reacts only with the P1 isoform on neutrophils. Direct treatment of HNA-3a–positive endothelial cells with anti–HNA-3a, but not with anti–HNA-3b, leads to reactive oxygen species production, increased albumin influx, and decreased endothelial resistance associated with the formation of actin stress filaments and loosening of junctional vascular endothelium-cadherin. In a novel in vivo mouse model, TRALI was documented by significant increase in lung water content, albumin concentration, and neutrophil numbers in the bronchoalveolar lavage on injection of human anti–HNA-3a in lipopolysaccharides-treated, as well as nontreated mice. Interestingly, although neutrophil depletion alleviated severity of lung injury, it failed to prevent TRALI in this model. Infusion of anti–HNA-3a F(ab′) 2 fragments caused moderate TRALI. Finally, mice lacking nicotinamide adenine dinucleotide phosphate oxidase (NOX2 y/ - ) were protected from anti–HNA-3a-mediated TRALI. Conclusions— These data demonstrate the initiation of endothelial barrier dysfunction in vitro and in vivo by direct binding of anti–HNA-3a on endothelial cells. It seems, however, that the presence of neutrophils aggravates barrier dysfunction. This novel mechanism of TRALI primarily mediated by endothelial cell dysfunction via choline transporter-like protein 2 may help to define new treatment strategies to decrease TRALI-related mortality.

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Section: Discussionmentioning

confidence: 99%

Anti–Human Neutrophil Antigen-3a Induced Transfusion-Related Acute Lung Injury in Mice by Direct Disturbance of Lung Endothelial Cells

Bayat

Tjahjono

Sydykov

et al. 2013

ATVB

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“…Despite the fact that most antibodies directed against NS1 have been found to provide some level of passive protection to mice from a lethal flavivirus challenge (Henchal et al, 1988Schlesinger, 1985Schlesinger et al, 1986), a small number have been shown to increase morbidity (Falconar, 1997(Falconar, , 2008Henchal et al, 1988). Since these early observations, anti-NS1 antibodies have been shown to cross-react with a wide range of host cell components including extracellular matrix, blood clotting and integrin/adhesion proteins, platelets as well as to ATP synthase β chain, protein disulfide isomerise (PDI), vimentin and heat shock protein on endothelial cells (Cheng et al, 2009;Falconar, 1997Falconar, , 2007Immenschuh et al, 2013;Lin et al, 2001;Lin et al, 2003;Lin et al, 2002;Lin et al, 2006;Sun et al, 2007). The induction of auto-antibodies relatively early in acute secondary dengue infections as part of the anamnestic antibody response, that can bind platelets and uninfected endothelial cells has suggested a possible role for these antibodies in the endothelial cell dysfunction that underlies the haemorrhage and vascular leak in DHF/DSS patients (Sun et al, 2007).…”

Section: Ns1 Induction Of Autoantibodies and A Potential Role In Pathmentioning

confidence: 99%

The flavivirus NS1 protein: Molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker

2013

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The flavivirus nonstructural glycoprotein NS1 is an enigmatic protein whose structure and mechanistic function have remained somewhat elusive ever since it was first reported in 1970 as a viral antigen circulating in the sera of dengue-infected patients. All flavivirus NS1 genes share a high degree of homology, encoding a 352-amino-acid polypeptide that has a molecular weight of 46-55 kDa, depending on its glycosylation status. NS1 exists in multiple oligomeric forms and is found in different cellular locations: a cell membrane-bound form in association with virus-induced intracellular vesicular compartments, on the cell surface and as a soluble secreted hexameric lipoparticle. Intracellular NS1 co-localizes with dsRNA and other components of the viral replication complex and plays an essential cofactor role in replication. Although this makes NS1 an ideal target for inhibitor design, the precise nature of its cofactor function has yet to be elucidated. A plethora of potential interacting partners have been identified, particularly for the secreted form of NS1, with many being implicated in immune evasion strategies. Secreted and cell-surface-associated NS1 are highly immunogenic and both the proteins themselves and the antibodies they elicit have been implicated in the seemingly contradictory roles of protection and pathogenesis in the infected host. Finally, NS1 is also an important biomarker for early diagnosis of disease. In this article, we provide an overview of these somewhat disparate areas of research, drawing together the wealth of data generated over more than 40 years of study of this fascinating protein.

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“…HO-1 is a potential therapeutic target in treating thrombotic disease and HO-1 knockout mice demonstrated acute thrombus formation in response to hypoxia 34 . Previous studies reported that dengue virus glycoprotein-1 (DV-NS1) antibody inhibited PDI activity and blocked platelet aggregation accompanied by an increase in HO-1 35 36 . Furthermore, redox reactions have been shown to play crucial roles in platelet aggregation in a glutathione peroxidase-3 (GPx-3)-deficient mouse model.…”

Section: Discussionmentioning

confidence: 99%

Novel anti-thrombotic agent for modulation of protein disulfide isomerase family member ERp57 for prophylactic therapy

Cui

Shan

Guo

et al. 2015

Sci Rep

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Protein disulfide isomerase (PDI) family members including PDI and ERp57 emerge as novel targets for anti-thrombotic treatments, but chemical agents with selectivity remain to be explored. We previously reported a novel derivative of danshensu (DSS), known as ADTM, displayed strong cardioprotective effects against oxidative stress-induced cellular injury in vitro and acute myocardial infarct in vivo. Herein, using chemical proteomics approach, we identified ERp57 as a major target of ADTM. ADTM displayed potent inhibitory effects on the redox activity of ERp57, inhibited the adenosine diphosphate (ADP)-induced expressions of P-selectin and αIIbβ3 integrin, and disrupted the interaction between ERp57 and αIIbβ3. In addition, ADTM inhibited both arachidonic acid (AA)-induced and ADP-induced platelet aggregation in vitro. Furthermore, ADTM significantly inhibited rat platelet aggregation and thrombus formation in vivo. Taken together, ADTM represents a promising candidate for anti-thrombotic therapy targeting ERp57.

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Antibodies against dengue virus nonstructural protein-1 induce heme oxygenase-1 via a redox-dependent pathway in human endothelial cells

Cited by 11 publications

References 42 publications

Anti–Human Neutrophil Antigen-3a Induced Transfusion-Related Acute Lung Injury in Mice by Direct Disturbance of Lung Endothelial Cells

Anti–Human Neutrophil Antigen-3a Induced Transfusion-Related Acute Lung Injury in Mice by Direct Disturbance of Lung Endothelial Cells

The flavivirus NS1 protein: Molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker

Novel anti-thrombotic agent for modulation of protein disulfide isomerase family member ERp57 for prophylactic therapy

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