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Recognition of nanoparticles by macrophages-from principles to consequences and toxicity.

Authors
Shvedova-AA
Source
Toxicologist 2012 Mar; 126(Suppl 1):177
NIOSHTIC No.
20040543
Abstract
Engineered nanomaterials (EN) have unique physico-chemical properties that make them promising for many biomedical applications. However, with the burgeoning capabilities to manipulate structures at the nano-scale, employing this machinery for safe and efficient drug delivery is not fully explored. To this end recognition of EN by the immune system, our primary defense outpost against foreign invasion is a critical point. Recognition versus non-recognition of EN by the immune system not only determines the distribution of nanomaterials in the body but may also dictate their toxic potential. Recent studies showed that autophagy may have emerged as the initial and primordial defense of eukaryotic cells against microbes. It is therefore not surprising that immune-competent cells may respond to EN in a similar manner as to viruses/bacteria. Consequently, there are complex relationships between the infection process and inflammatory responses to EN resulting in potent effects of nanoparticles on pulmonary clearance of bacteria. Elucidation of how EN impact the conserved mechanism of autophagy, recognition and/or phagocytosis promise to be an interesting and fruitful area for better understanding of interactions of EN with the cells of innate immune system, particularly macrophages. It becomes clear that the presence of specific recognition patterns primarily defined by the EN' size and charges are essential for their recognition and uptake by macrophages. Further, the presence of specific signals on the surface of EN, such as adsorbed lipids or proteins, confers additional features to the effectiveness of the recognition of nanoparticles by professions phagocytes. Finally, oxidative stress - known to act as an underlying mechanism that drives the toxicities of EN in vitro as well as in vivo - may be triggered as a macrophage response to recognized nanoparticles. Overall, the mechanisms of recognition, cellular internalization of EN by immune competent cells, particularly macrophages, represent an important new field of molecular nanotoxicology.
Keywords
Nanotechnology; Particulates; Toxic-materials; Health-hazards; Biohazards; Biomedical-engineering; Immune-reaction; Immune-system; Autoimmunity; Cell-function; Microorganisms; Pulmonary-clearance; Bacteria; Phagocytic-activity; Cellular-uptake; Oxidative-processes; Toxic-effects
Publication Date
20120301
Document Type
Abstract
Fiscal Year
2012
NTIS Accession No.
NTIS Price
Identifying No.
B04132012
ISSN
1096-6080
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
State
WV; CA
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