The Effect Of Aquatic Environmental Processes On Nano-vanadium Dioxide And Graphene Oxide’s Immunotoxicity

The widespread use of engineered nanomaterials, such as carbon nanomaterials, silver nanoparticles (nano-Ag), titanium dioxide nanoparticles (nano-TiO2) and other metal and metal oxide nanoparticles, has raised concerns about their possible adverse effects to the environment. Nowadays, engineered nanomaterials, which have been detected in the environment within some place at a relative high concentration, are found to be directly deleterious to living organisms, as well as accumulate and transfer along food chains leading to cumulative toxicity. More important, studies showed clearly that the property and related toxicity of nanomaterials could be changed significantly after released into environment, especially into water systems. Therefore, it’s vitally important to carry out research on the change of physicochemical properties of engineered nanomaterials in water systems and its ensuing biological effects.Additionally, based on the recognition of self and nonself, immune system can help organisms to defend against alien invasion in order to protect themselves. So, it is of high importance to study more aspects of the immunological effects induced by nanomaterials and how these modulations occur.We studied the adverse effect of nanomaterials by focusing on the two aspects.(1) The acidic transformed nano-vanadium dioxide (abbreviated as nano-VO2or nVO2) caused macrophage cell death by the induction of lysosomal membrane permeabilization and Ca2+effluxBecause of the outstanding thermochromic characteristics and other changes during phase transition, nano-VCO2has been applied wildly in electrical and optical devices, and design of intelligent window. Although research on vanadate ions and other forms of compounds that contain vanadium is long-standing, little has been known about the biological effect of nano-scaled VO2, especially when it was released into the environment during manufacturing, production and consumer process. By studying the toxicity of nano-VO2altered by environmental factor of pH, we showed in the present study that though no obvious toxic effect of nano-VO2on mammalian cells was found during short-term exposure, it was certain that upon exposure in acidic water condition, nano-VO2could transform to new transformation product as revealed by TEM, which could rapidly induce macrophage cell death while hardly affect the survival of common epithelial cell. Further investigation revealed that this transformation product caused macrophage apoptosis by the induction of Ca2+efflux and later the mitochondrial membrane permeabilization (MMP). Moreover, a more detailed time course study indicated that this product could cause lysosomal membrane permeabilization (LMP) at the earlier stage, indicating LMP might be used as an earlier and sensitive end point for nanotoxicological study. We concluded that although nano-VO2did not show an acute toxicity, its transformation product in acidic water could induce macrophage apoptosis by the induction of lysosomal membrane permeabilization (LMP) and Ca2+efflux.(2) Graphene oxide modulates B cell surface phenotype and impairs plasma cell immunoglobulin secretionSince discovery, graphene oxide (GO) has been used in all aspects of human life and revealed promising applications in biomedicine. Nevertheless, the potential risks of GO were always being revealed. Although GO was found to induce immune cell death and innate immune response, little is known regarding its toxicity to the specific adaptive immune system that is crucial for protecting against exotic invasion. The B-cell mediated adaptive immune system, which composed of highly specialized cells (B and plasma cell) and specific immune response (antibody response) is the focus in our present study. Using diverse standard immunological techniques, we found that GO modulated B cell surface phenotype, both costimulatory molecules (CD80, CD86and especially CD40) and antigen presenting molecules (both classical and nonclassical) under the condition without causing cell death. Meanwhile, the terminal differentiated immunoglobulin (Ig) secreting plasma cell was affected by GO, which displayed a less secretion of Ig and more severe ER stress caused by the retention of the secreted form of Ig in cell compartment. The combined data reveal that GO has a particular adverse effect to B cell and the humoral immunity, directly demonstrating the potential risk of GO to the specific adaptive immunity.From our results, the importantance of the two aspects (water environmental processes and immunotoxicity) of the study on adverse effect of nanomaterials was displayed clearly.