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Comprehensive assessment of hazardous effects of engineered nanomaterials on the immune system

Periodic Report Summary - NANOMMUNE (Comprehensive assessment of hazardous effects of engineered nanomaterials on the immune system)

NANOMMUNE and its consortium
The NANOMMUNE project, funded by the European Commission through the Seventh Framework Programme, was launched on 1 September 2008 and will run for three years. The NANOMMUNE consortium is coordinated by Karolinska Institutet, one of the leading medical universities in Europe. A total of 13 principal investigators belonging to 10 different partner institutes are included in the consortium (Karolinska Institutet (KI)- Bengt Fadeel and Annika Scheynius; Royal Institute of Technology (KTH)- Mamoun Muhammed; Uppsala University (UU)- Maria Stromme; University of Cologne (UCO)- Sanjay Mathur; University of Turku (UT)- Riitta Lahesmaa; Swiss Federal Laboratories for Materials Testing and Research (EMPA)- Harald Krug; Institute of Occupational Medicine (IOM)- Lang Tran; University of Pittsburgh (UP)- Valerian Kagan, Alexander Star; National Institute for Occupational Safety and Health (NIOSH)- Anna Shvedova; North Carolina State University (NCSU)- Nancy Monteiro-Riviere and Jim Riviere).

Description of the work performed since the beginning of the project
The management office (WP1) was set up at Karolinska Institutet and a project website has been constructed (see online). Kick-off and consortium meetings were also held. For the scientific work during the first 18 months, the main activities were concentrated to WP2 (material synthesis and characterisation) and WP3 (in vitro assessment of ENs). To date, nanomaterials of 15 different systems have been studied. A number of standard operating procedures (SOPs) were established for material synthesis and characterisation, and for in vitro assessment of nanomaterials. Several original and review articles were published, including one review in Annual Review of Pharmacology and Toxicology, the leading journal in the field.

Description of the main results achieved so far
Previous studies on macrophage recognition of apoptotic cells have revealed that the exposition of the phospholipid, phosphatidylserine (PS) on the surface of apoptotic cells serves as an important recognition signal for phagocytic cells. Four NANOMMUNE partners in Europe and the United States have now shown that coating of single-walled carbon nanotubes (SWCNT) with the 'eat-me' signal, PS makes nanotubes recognisable by macrophages, including primary human monocyte-derived macrophages and dendritic cells (Konduru et al., PLoS-ONE, 2009). Furthermore, project partners at the University of Pittsburgh reported on horseradish peroxidase-catalysed degradation of SWCNT (Allen et al., J. Am. Chem. Soc., 2009). These results mark a promising possibility for carbon nanotubes to be degraded in the environment. In addition, two NANOMMUNE partner institutes have reported on the interactions between mesoporous silica particles with human monocyte-derived macrophages (Witasp et al., Toxicol. Appl. Pharmacol., 2009). These findings are relevant to the development of mesoporous materials for drug delivery and other biomedical applications. Finally, several partners have played an active role in the dissemination of project results (WP7).

Expected final results and their potential impact and use
The multidisciplinary approach of the current project will contribute to the elucidation of the hazardous effects of ENs on the immune system, and will enable reliable and sound assessment of the risks to human health posed by these materials. Our studies will benefit:
a) citizens, because we address issues related to human health;
b) researchers, because we will generate new knowledge in material production, and on mechanisms of interaction of nanomaterials with biological systems; and
c) industry (including SMEs), because we plan to incorporate our characterisation protocols into a quality handbook, which can provide support to interested parties.