ReviewImmunotoxicity of nickel: Pathological and toxicological effects
Graphical abstract
Introduction
Nickel (Ni) is an abundant metal in the Earth's crust and is the 24th most abundant element. Also, Ni is nutritionally regarded as an essential trace element for many animal species, plants, and microorganisms (Chivers, 2015; Genchi et al., 2020; Shahzad et al., 2018; Zambelli and Ciurli, 2013). Because of its unique chemical properties, Ni has extensive applications in various modern industrial fields, such as refining, electroplating, welding, electroforming, and the production of nickel-cadmium batteries (Binet et al., 2018; Schaumloffel, 2012). The consumption of products containing Ni has resulted in environmental pollution by Ni and its compounds. With increasing incidences of Ni contamination over recent years, the toxicity of Ni has also attracted more attention (Filatova and Cherpak, 2020; Lyu et al., 2019; Zambelli et al., 2016; Zhang et al., 2019). Many studies have suggested that Ni exposure can result in various adverse health effects, such as developmental toxicity, genotoxicity, immunotoxicity, haematotoxicity, reproductive toxicity, and neurotoxicity (Denkhaus and Salnikow, 2002; Doll, 1984; Dumala et al., 2019b; Guo et al., 2016b, 2016c; Rizvi et al., 2020; Zhang et al., 2019, 2020). Furthermore, oxidative stress, apoptosis, and DNA damage are important molecular mechanism underlying Ni toxicology (Guo et al., 2016a, 2019b). In 1950, the carcinogenic effects of Ni and its compounds have been recognized and reported (Bidstrup, 1950). Several epidemiological reports showed that Ni exposure because of occupational needs results in a higher prevalence of nasal and lung cancers in humans (Cempel and Nikel, 2006; Das et al., 2008; Kalagbor et al., 2019). In 1990, Ni and its compounds have been classified as group 1 carcinogens (i.e., confirmed carcinogen) to humans by the International Agency for Research on Cancer (IARC) (Scarselli et al., 2018).
Until now, a large body of scientific evidence summarizes the deleterious effect of Ni on the immune system (Petersen et al., 2019; Singh et al., 2019). Ni immunotoxicity potentially forms a significant part of Ni carcinogenesis in various tissues since it decreases immune surveillance. Previous research showed that nickel chloride (NiCl2) impairs the immune system of broiler chickens (Huang et al., 2014; Tang et al., 2015; Wu et al., 2013, 2014a; Yin et al., 2016a). NiCl2 has been shown to inhibit the development of immune organs and increase lymphocyte apoptosis (Huang et al., 2013; Tang et al., 2014, 2015; Wu et al., 2014a; Yin et al., 2016a). It has also been shown that Ni exerts toxic effects on the growth of macrophages and B cells in vitro (Guo et al., 2019a; Lou et al., 2013; Sunderman et al., 1989; Taira et al., 2008; Volke et al., 2013). While many studies have shown that Ni in fact imparted immunotoxicity, the underlying mechanism still remains unclear, and no evidence is available on the effect of Ni on bone marrow and complement systems. The goal of this review therefore is to summarize recent research about the immunotoxicity of Ni, including the development of organs of immune system, lymphocyte subpopulations, cytokines, immunoglobulins, natural killer (NK) cells, and macrophages, and also allergic contact dermatitis. This review will be helpful for the identification of defects in the mechanisms underlying Ni toxicity, and will provide a theoretical basis for the prevention and treatment of Ni-related carcinogenicity and toxicology.
Section snippets
Source of Ni exposure
Ni belongs to group VIII B in the periodic table (Cempel and Nikel, 2006), is widely distributed, and is released from both natural and anthropogenic sources. Ni can occur in the water, air, soil, and biological materials. In the atmosphere, Ni originates from dust blown by wind, volcanic emissions, weathering products of soils and rocks, wild fires, and vegetation (Das et al., 2018). Ni exists in nature either in insoluble particles, such as nickel sulfides (e.g., NiS and Ni3S2), oxides (NiO),
Effect of Ni on the organs of immune system
The immune system comprises of organs that control the production and maturation of lymphocytes. Over recent decades, great attention has been paid on the roles of Ni in the modulation of immune system. Previous works have confirmed that Ni and its compounds can impair immune organs, such as thymus, spleen, bursa of Fabricius and cecal tonsil (Supplemental Table 1).
Effect of Ni on lymphocyte subpopulations
Immunophenotyping of the lymphocytes of the blood serves as a key instrument for the diagnosis of immunologic and hematologic disorders (Deneys et al., 2001). Evidence from recent past indicates that Ni greatly influences many subpopulations of immune cells (Salsano et al., 2004). The population of T lymphocytes is a crucial decisive factor for cellular immunity (Zuluaga et al., 2016). As an essential component of cell-mediated immunity, T lymphocytes can be further categorized into many
Effect of Ni on cytokines
The immune system is a complex network consisting of single cells, lymphoid tissues and organs, and cell aggregations. To achieve a coordinated immune response, effective communication within the network is needed, which is accomplished by cytokines (Brodin and Davis, 2017). Cytokines regulate lymphocyte proliferation and differentiation, cell trafficking and inflammation, and lymphoid development (Huang et al., 2005). Th1 helper cells increase the responses mediated by cells, particularly to
Effect of Ni on immunoglobulins
Recent studies that evaluated antibody levels of Ni-exposed individuals reported conflicting results (Table 3). Singh et al. (2019) reported no changes in serum total immunoglobulin (Ig) and IgG concentrations in female hariana heifers in response to exposure to 3.0 mg of Ni/kg. However, another study reported that ingestion of NiSO4 could depress the responses of IgG and IgM antibodies against keyhole limpet hemocyanin (KLH) injection in mice (Schiffer et al., 1991). A previous study also
Effect of Ni on NK cells and macrophages
Macrophages and NK cells exert a significant function in immunity and immune responses (Gordon, 2003; Vivier et al., 2008). They assume a defensive role in the phagocytosis of parasites and microbes. It has been shown that Ni can affect the activity and survival of macrophages and NK cells (see supplementary Table 2). Mice injected with NiCl2 showed suppressed activities of splenic NK cells and phagocytic activities of resident peritoneal macrophages (Smialowicz et al., 1984, 1985). Systemic
Conclusions
This review summarizes recent research on Ni immunotoxicity. Excessive Ni exposure can inhibit immune organ development by inducing excessive apoptosis and proliferation inhibition. Moreover, while Ni can decrease T and B lymphocytes, the specific underlying mechanism requires further research. Effects of Ni on IgA, IgG, and IgM were elusive. Ni inhibited IgA, IgG, and IgM levels in animal experiments but the opposite result was found in human research. Also, Ni inhibited the production of
Declaration of competing interest
The authors declare that there are no conflicts of interest.
Acknowledgment
This research was supported by the program for Changjiang scholars and the university innovative research team (IRT 0848), and the Shuangzhi project of Sichuan Agricultural University (03572437; 03573050).
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2023, Urban ClimateCitation Excerpt :Guo et al. (2020), when studying the toxicological effects harmful to human health caused by Ni, identified underlying harm related to its immunotoxicity, and Ni may be extremely carcinogenic in the population. When comparing the harmful effects on human health caused by the chemical elements of Ti, V and Ni identified in this study, with other highly relevant research (Ferraro et al., 2020; Guo et al., 2020; Desaulniers et al., 2021), it is highly recommended that the authorities in Budapest create public policies that involve mitigating atmospheric pollution, considering that the current risks of contamination by ultra-fine particles (containing Hg, As, Cd, Pb and other toxic elements) suspended in the air is very real and capable of permanently compromising the quality of urban living. The presence of the chemical composition of carbonaceous particles smaller than 100 nm was highly diversified, containing especially dangerous elements such as: silver (Ag), arsenic (As), barium (Ba), carbon (C), cadmium (Cd), chlorine (Cl), cobalt (Co), chromium (Cr), mercury (Hg), germanium (Ge), manganese (Mn), magnesium (Mg), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), tin (Sn), strontium (Sr), titanium (Ti), vanadium (V), tungsten (W), zinc (Zn), and zirconium (Zr) (Table 2).
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These authors contributed equally to this work.