Mechanism of immunosuppression in zebrafish (Danio rerio) spleen induced by environmentally relevant concentrations of perfluorooctanoic acid. (June 2020)

• Record Type: Journal Article
• Authors: Zhong, Yuchi; Shen, Lilai; Ye, Xueping; Zhou, Dongren; He, Yunyi; Zhang, Hangjun
• Is Part Of: Chemosphere. Volume 249(2020)
• Publication Date: 2020-06
• Subjects: Immunotoxicity -- Perfluorooctanoic acid -- Spleen -- Cytokine -- Immunoglobulin -- NF-Kappa B; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2020.126200
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Perfluorooctanoic acid (PFOA) has been identified as a new persistent organic pollutant. This pollutant is ubiquitous in water and environments. Although PFOA is toxic to fishes, the precise immunotoxicological mechanism remains unclear. In this study, HPLC-MS analysis proved that PFOA can accumulate in the spleen of zebrafish. As comparison of 7-day and 14-day data, the cumulative content in the spleen significantly increased by 26% even in the 0.1 mg/L PFOA-treated group. Morphological observations revealed that PFOA can damage immune cells in zebrafish spleen by inducing vacuolization, lipofuscin granule production, and mitochondrial swelling. The Toll-like receptor 2 (TLR2)/myeloid differentiation factor 88 (myd88)/NF-κB (P65) pathway can mediate the mRNA expression levels of interferon (IFN) and B cell-activating factor (BAFF); immunoglobulin (Ig) secretion is further regulated. RT-PCR results indicated that the expression levels of P65 and IFN in the 1 mg/L group after PFOA exposure for 7 d increased by 4.03- and 3.28-fold, respectively, in a dose-dependent manner compared with those of the control group. The linear correlation coefficient ( r 2 ) was analyzed, and the results indicated that the Ig-mediated pathway can be affected by PFOA. For example, the r 2 between IgD and P65 decreased from 0.641 (7 d) to 0.295 (14 d) after the cells were exposed to PFOA for a prolonged time; the r 2 between IgD and IFN increased from 0.562 (7 d) to 0.808 (14 d). The triangle plot method strongly demonstrated that increased PFOA concentration and prolonged exposure to PFOA can inhibit Ig secretion. Therefore, immune organs, particularly the spleen, of zebrafish are vulnerable to PFOA. These results can help to improve the understanding of the possible noncarcinogenic risk mechanisms induced by PFOA. Graphical abstract: Image 1 Highlights: Environmentally relevant concentrations of PFOA can accumulate in the spleen of zebrafish. PFOA can enhance immunoglobulin secretion deprivation in a dose- and exposure-dependent manner. PFOA disrupts immunoglobulin levels by activating the TLR/myd88/P65 pathway. PFOA disrupts immunoglobulin levels by interfering with IFN and BAFF mRNA expression. PFOA-induced lipid metabolism disorder enhances the immune toxicity level in the spleen.