In Vitro Multibiomarker Approaches for Assessing the Immunotoxicity of Certain Sections in Yangtze River

Abstract

Due to multiple endpoints and complex mechanisms, immunotoxicity tests were scarcely applied to environmental matrices. In this study, using a high-content screening system, a series of high-throughput multibiomarker approaches based on the immune functions of THP-1 macrophages (cell adhesion, morphology, phagocytosis, and production of multiple cytokines/chemokines) were adopted to evaluate the immunotoxicity of surface water extracts from the Yangtze River (near the Nanjing Chemical Industrial Park). The results suggested that the cell morphology and adhesion of macrophages were sensitive and appropriate for evaluating the surface water quality since both were closely associated with inflammation initiation and altered significantly when treated with only 10× water extracts. Twenty-four hours of exposure with water organic extracts (10× and 50×) suppressed cell phagocytosis, which was similar to the results of surface water extracts from southern Korea. Additionally, 30 cytokines/chemokines (including inflammatory cytokines; mediators of macrophages, T cells, and other immune cells; regulating neurons, angiogenesis, and anti-infection processes) were significantly altered by 50× water extracts. The top 10 cytokines are recommended as potential candidates for indicating surface water immunotoxicity. This research is the first study to evaluate many immunotoxicity endpoints with surface water extracts and offers fresh insights into the in vitro immunotoxic evaluation methods.

Chlorinated Polycyclic Aromatic Hydrocarbons Induce Immunosuppression in THP-1 Macrophages Characterized by Disrupted Amino Acid Metabolism

“…First, the immunotoxicity of Cl-PAH/PPAHs was detected with an in vitro immunotoxicity screening system based on HCS technology (detailed schematic shown in Figure S1). The immunophenotypic information was obtained with several cytological profiling assays, which were performed as previously reported. ,, Second, the global metabolomics profiles altered by Cl-PAH/PAHs were collected with HRMS LC–MS/MS and statistically analyzed. Finally, the association between metabolomics information and immune phenotypes was conducted and the potential biomarkers of immunometabolism were identified.…”

Immunotoxicity In Vitro Assays for Environmental Pollutants under Paradigm Shift in Toxicity Tests

“…There have been several functional assays described above, and the first task is to find a stable cell line that could replace animal cells. It is based on this idea that our team used THP-1-derived Mϕs, detecting phagocytosis, adhesion, cell morphology and cytokine production, and applied it for the first time in the immunotoxicity detection of Yangtze River samples [96], providing a reference for the development of in vitro immunotoxicity detection methods. However, because of the complexity of the immune system, there is no single method that is completely accepted and standardized for pollutant assessment by OECD or EPA, resulting a in decrease in data comparability, and a difficulty in the toxicity prediction of an unknown material.…”