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T. Rakovich
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-031 - Induction of Protein Citrullination and Auto-Antibodies Production in Murine Exposed to Nickel Nanomaterials (ID 2827)
09:30 - 09:30 | Author(s): T. Rakovich
- Abstract
Background:
Citrullination, or the post-translational deimination of polypeptide-bound arginine, is involved in several pathological processes in the body, including autoimmunity and tumorigenesis. This enzymatic conversion is governed by the family of Ca[2+]-dependent peptidylarginine deiminases (PAD). Citrullinated proteins are recognised as non-self-proteins, and subsequently can induce an autoimmune response. Recent studies have shown that nanomaterials of diverse origin can trigger protein citrullination, which might constitute a common pathogenic link to disease development.
Methods:
Engineered nickel nanomaterials, which can mimic environmental filamentous materials were hypothesised to trigger similar pathophysiological responses. Mice were injected intraperitoneally with either nickel nanomaterials or phosphate buffered saline. Murine sera samples for anti-CCP3 detection and tissue samples for immunohistochemical analysis were collected at day 1 and day 14.
Results:
Auto-antibody production was detected in serum of nickel nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels were found to be elevated in nanomaterials -treated cell lines as well as in the spleen, kidneys and lymph nodes of mice, suggesting a systemic response to nickel nanomaterials injection, and validated in human pleural and pericardial malignant mesothelioma (MM) samples.
Conclusion:
The observed systemic responses in mice exposed to nickel nanomaterials support the evidence linking exposure to environmental factors with the development of autoimmunity responses and reinforces the need for comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials induce pathological processes that mimic those observed in Pleural MM, and therefore require further investigations into their carcinogenicity.
