Treatment of Paraquat-Induced Lung Injury With an Anti-C5a Antibody: Potential Clinical Application*

Sun, Shihui; Jiang, Yuting; Wang, Renxi; Liu, Chenfeng; Liu, Xiaoling; Song, Nianping; Guo, Yan; Guo, Renfeng; Du, Lanying; Jiang, Shibo; Li, Yan; Qiu, Zewu; Zhao, Guangyu; Zhou, Yusen

doi:10.1097/ccm.0000000000002950

Cited by 23 publications

(18 citation statements)

References 41 publications

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“…TIIA attenuates decreased expression levels of Ang- (1)(2)(3)(4)(5)(6)(7) in in the lung tissues of rats with PQ-induced ALI. Expression levels of Ang-(1-7) were demonstrated to be significantly suppressed in the PQ group compared with the control group; however, the expression of Ang-(1-7) was significantly increased in the PQ + TIIA group compared with the PQ group ( Fig.…”

Section: Tiia Attenuates Increased Ldh and Protein Levels As Well Asmentioning

confidence: 97%

“…Acute lung injury (ALI) is a common disease with a high morbidity and mortality rate worldwide (1)(2). More than 2 million ALI cases caused by chemical poisoning including paraquat are reported annually in China, resulting in over 150,000 deaths (1). Numerous factors may induce ALI, including pathogens, toxins, infections and autoimmune factors (1).…”

Section: Introductionmentioning

confidence: 99%

“…More than 2 million ALI cases caused by chemical poisoning including paraquat are reported annually in China, resulting in over 150,000 deaths (1). Numerous factors may induce ALI, including pathogens, toxins, infections and autoimmune factors (1). A number of previous studies have revealed that acute inflammation and oxidative stress are involved in the development of ALI (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

“…A number of previous studies have revealed that acute inflammation and oxidative stress are involved in the development of ALI (2)(3)(4). Numerous animal models of ALI have been established to investigate the pathogenesis of this disease and to develop novel therapeutic treatments (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

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Tanshinone IIA attenuates paraquat‑induced acute lung injury by modulating angiotensin‑converting enzyme 2/angiotensin‑(1‑7) in rats

Wang

Niu

et al. 2018

Mol Med Report

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Tanshinone IIA (TIIA) is an active compound that can be isolated from the Chinese herb, Salvia miltiorrhizae Bunge, also known as danshen. Previous studies have demonstrated that TIIA can effectively attenuate bleomycin‑induced pulmonary fibrosis in rats. However, it has not been determined whether TIIA can attenuate paraquat (PQ)‑induced acute lung injury (ALI). In the present study, the protective effects exhibited by TIIA on PQ‑induced ALI, as well as its underlying mechanisms, were investigated using Sprague‑Dawley (SD) rats. ALI animal models using rats were established via administration of PQ. Adult male SD rats were randomly divided into three groups: A control group, a PQ group and a PQ + TIIA group. Total cell count, total protein levels and lactic dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF), as well as myeloperoxidase (MPO) activity in lung tissues were determined. Lung histological alterations were also investigated. Angiotensin converting enzyme 2 (ACE2) and Angiotensin 1‑7 [Ang‑(1‑7)] expression levels in the lung were also analyzed. The results demonstrated that administration of PQ induced marked histological alterations, and markedly increased neutrophil infiltration, lung wet/dry weight ratio, total cell count, protein content and LDH levels in BALF. In addition, PQ was revealed to significantly decrease ACE2 and Ang‑(1‑7) expression levels in lung tissues. However, it was demonstrated that TIIA attenuated these effects. Therefore, the results of the present study suggest that that TIIA may exhibit a therapeutic effect regarding PQ‑induced ALI in rats, and that ACE2 and Ang‑(1‑7) may be involved in the underlying mechanisms of this effect.

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Section: Tiia Attenuates Increased Ldh and Protein Levels As Well Asmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tanshinone IIA attenuates paraquat‑induced acute lung injury by modulating angiotensin‑converting enzyme 2/angiotensin‑(1‑7) in rats

Wang

Niu

et al. 2018

Mol Med Report

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“…IFX-1 is a monoclonal antibody that blocks the effect of C5a and, therefore, keeps the formation of the MAC intact by not interfering with C5b generation or function (106). It has shown efficacy in nonhuman primate models of toxin-and virus-induced acute lung injury (107,108). Avdoralimab (IPH5401) is an IgG1-κ anti-C5aR1 blocking antibody that has previously been used in phase I and II studies in combination with checkpoint inhibitors for solid tumors (NCT03665129) and is being studied in patients with COVID-19 (NCT04371367) who need ≥5 L/min supplemental oxygen to maintain oxygen saturation (SpO2) >93% or those with ARDS, who need invasive mechanical ventilation with a PaO2/FiO2 ratio <300 for more than 24 hours.…”

Section: Targeting Complement: Current and Future Trialsmentioning

confidence: 99%

The complement system in COVID-19: friend and foe?

Java¹,

Apicelli²,

Liszewski³

et al. 2020

JCI Insight

331

387

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Interplay between SARS-CoV-2 and the complement system Antiviral strategies. The complement system traces its origins to more than a billion years ago when primitive proteins evolved to protect cells from pathogens and to engage in intracellular metabolic processes (18, 19) (Figure 1A). The contemporary complement system lies at the interface between innate and adaptive immunity (20). It efficiently recognizes and eliminates viral pathogens via several mechanisms: opsonizing viruses and virus-infected cells (including lysing them), inducing an antiviral immunoinflammatory state, boosting virus-specific immune responses, and directly neutralizing cell-free viruses (21) (reviewed in ref. 22). Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19-related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19; (d) a subset of patients with COVID-19 may have a genetic predisposition associated with complement dysregulation; and (e) these observations create a basis for clinical trials of complement inhibitors in life-threatening illness.

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Immunotoxicology in Industrial Hygiene and Occupational Exposures

2023

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Immunotoxicology is the study of drugs and chemicals that produce adverse effects on the immune system. Adverse immune effects include suppression, leading to compromised ability to fight infections, or enhancement, which could be involved in hypersensitivity (allergy) or autoimmunity. It has been appreciated for hundreds of years that diseases are associated with various occupations, such as respiratory diseases in those working with grains, coal, metals, or animals. We now understand that many of these occupational diseases are the result of an unregulated immune response to a specific agent. Similarly, occupational exposures to various chemicals can produce dermatitis, again due in part to unregulated immune responses in the skin. Additionally, occupational chemical exposures have been demonstrated to induce immune suppression. This chapter provides an overview of the immune system, a synopsis of standard assays to evaluate immunotoxic potential of occupational chemicals, and descriptions of effects of several occupational immunotoxicants with a focus on human exposures and doses. Consideration is given to current data gaps and potential use of novel technologies to more precisely define effects and mechanisms of occupational immunotoxicants.

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Treatment of Paraquat-Induced Lung Injury With an Anti-C5a Antibody: Potential Clinical Application*

Abstract: Supplemental Digital Content is available in the text.

Cited by 23 publications

References 41 publications

Tanshinone IIA attenuates paraquat‑induced acute lung injury by modulating angiotensin‑converting enzyme 2/angiotensin‑(1‑7) in rats

Tanshinone IIA attenuates paraquat‑induced acute lung injury by modulating angiotensin‑converting enzyme 2/angiotensin‑(1‑7) in rats

The complement system in COVID-19: friend and foe?

Immunotoxicology in Industrial Hygiene and Occupational Exposures

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