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Al Dhanhani, Mohamed, Sarawathiamma, Merin, Fernandez-Cabezudo, Haik, and Al-Ramadi: Systemic exposure to metallic nanoparticles initiates an acute, inflammasome-mediated, inflammatory response

Introduction: Nanoparticles are widely used in industry, electronics, cosmetics and biomedicine. However, there is evidence that chronic exposure to nanoparticles made of inorganic metal oxides or carbonaceous particles in air pollutants leads to pulmonary inflammatory disease. Previously, we demonstrated that intraperitoneal inoculation of inorganic metal nanoparticles leads to acute liver toxicity, manifested by a deposition of nanoparticles in the liver accompanied by significant rise in liver enzyme levels in the serum.

Objectives: This study investigated the nature of the in vivo inflammatory response associated with systemic administration of composite inorganic nanoparticles to wild-type C57BL/6- or NALP3-deficient mice.

Materials and methods: Groups of age-matched, male C57BL/6- or NALP3-deficient mice (four mice per group) were inoculated, via intraperitoneal injection, with composite metallic nanoparticles (1 mg/kg body weight), thioglycollate (4%) or line. Twenty-four hours later, peritoneal exudate cells were harvested by peritoneal lavage. Cells were then stained with a combination of monoclonal antibodies (including CD3, CD19, CD11b, F4/80, Ly6G, MHC class II, CD40, CD80 and CD86) and analysed by six-colour flow cytometry. In addition, RNA was extracted from the collected cells and the level of gene expression was determined for IL-1β, TNF-α and IL-6 by real-time polymerase chain reaction.

Results: Exposure to nanoparticles resulted in a tremendous recruitment and activation of myeloid cells, including mature macrophages and granulocytes. In addition, gene expression analysis revealed that nanoparticle injection up-regulates expression of IL-1β and TNF-α but not IL-6 genes. The inflammatory response to nanoparticle exposure was significantly reduced in NALP3-deficient mice.

Conclusion: Systemic exposure to metallic nanoparticles leads to a rapid inflammatory response characterized by the recruitment and activation of myeloid cells. This innate immune response is largely dependent on the NALP3 inflammasome. These findings highlight the need for further studies aimed at reducing the potential immunotoxicity associated with the use of nanoparticles in biomedicine.

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