Exposure of Mouse Peritoneal Resident Macrophages to Pristine MWCNT Promote Nitric Oxide Synthase Production and Acute Cytokine Response Flaviu TABARAN 1,2 *, Teodora MOCAN 2 , Lucian MOCAN 2 , Cristian T. MATEA 2 Andras NAGY 1 , Marian TAULESCU 1 , Adrian Florin Gal 1 , Cornel CĂTOI 1 1 Department of Anatomic Pathology, University of Agricultural Sciences and Veterinary Medicine Cluj- Napoca, Romania, 2 Regional Institute of Gastroenterology and HepatologyProf.Dr. “O. Fodor”, Cluj- Napoca, Romania *Corresponding author e-mail: alexandru.tabaran@usamvcluj.ro Bulletin UASVM Veterinary Medicine 71(2) / 2014, Print ISSN 1843-5270; Electronic ISSN 1843-5378 DOI:10.15835/buasvmcn-vm: 10866 Abstract Thepotentialbiomedical applicationsof carbon nanotubesare greatlylimited due to thegrowing evidences of their toxic effects on consumers. Recently, the cells of the monocyte-macrophage-system were observed to be the main structures of accumulation and toxicity of these nanomaterials.This study aimed to determine the changes in the inϐlammatory status and apoptosissuffered by macrophages following exposure to pristine multi-walled carbon nanotubes (MWCNT). Macrophages were isolated from the mouse peritoneum and cultivated in vitro following a protocol previously described by Zhang et al.(2008). The immunocytochemicalexpression of iNOs, IL-6 and apoptosis was measured by ϐluorometry usingConfocal laser scanning microscopy (CLSM). Exposure of peritoneal macrophages to MWCNT promotesiNOs production and IL-6 expression in a dose- related matter. The exposure to 10 and 25 μg/dl MWCNTdoes not induce apoptosis in macrophage culture, although a signiϐicant increase in numbers of cellsundergoing apoptosis is observed for the group exposed at 50μg/dl MWCNT. In the present research we demonstrated that exposure of mouse macrophages to pristine MWCNTpromote nitric oxide synthase production and an acute cytokine responsecharacterized by the elevation of IL-6 levels. Apoptosis is increased only at high levels of MWCNT exposure, being in respect of our results, a late expression of toxicity. Keywords: carbon nanotubes, inϔlammation, peritoneal macrophages INTRODUCTION Carbon nanotubes (CNT) are nanoscale cylindrical graphene sheets from the fullerene family being discovered by Iijima Japanese scientist in the early nineties. Since then, due to extraordinary proprieties, remarkable work was made in the implementation of these new generation materials in various ϐields, from basic material science to nanomedicine. This increasing production and the widespread application of these nanomaterials provides multiple sources of contamination for humans, thereby raising concern about the interaction between nanomaterials and living beings mainly about the risk that these materials have on humans This concern is maintained by the conϐlicting conclusions of the toxicological studies, results which are difϐicult to be grouped under a single, deϐinitive conclusion. Thus, the toxicological results varies between studies from mesotheliomas (Poland, 2008) and acute lethality following airborne exposure (Chiu- Wing, 2004) to the lack of any changes in the body that could indicate toxicity (Kam 2005). Nevertheless, one of the main ideas which are constantly validated in the pristine carbon nanotube toxicology reports are their accumulation in the cells of the monocyte-macrophage system (MM), mainly in ϐixed macrophages, the main