David M. Goncalves

Rafael de Liz

Denis Girard

The Inflammatory Process in Response to Nanoparticles

The use of nanoparticles (NPs) has increased in the past few years in various fields, including defence, aerospace, electronics, biology, medicine, and so forth. and in applications such as diagnostic technology, bioimaging, and drug/gene delivery. Thus, human exposure to NPs and nanomaterials is unavoidable and will certainly expand in the future resulting in a growing interest in nanotoxicology, the study of toxicity of nanomaterials. A number of studies have reported the effects of NPs in respect to pulmonary inflammation by investigating in vitro activation of pulmonary cells with NPs and in vivo in a variety of models in which neutrophils appear to be the predominant leukocyte cell type in lungs and in bronchoalveolar lavages following inhalation or intratracheal instillation of NPs. Despite the fact that several studies have reported an increased number of neutrophils, the literature dealing with the direct activation of neutrophils by a given NP is poorly documented. This paper will summarize the current literature in this latter area of research and will end with a perspective view in which our laboratory will be involved in the following years.

Activation of Neutrophils by Nanoparticles

Accumulating studies in animals have shown that nanoparticles could cause unusual rapid lung injury and extrapulmonary toxicity. Whether exposure of workers to nanoparticles may result in some unexpected damage as seen in animals is still a big concern. We previously reported findings regarding a group of patients exposed to nanoparticles and presenting with an unusual disease. The reported disease was characterized by bilateral chest fluid, pulmonary fibrosis, pleural granuloma, and multiorgan damage and was highly associated with the nanoparticle exposure. To strengthen this association, further information on exposure and the disease was collected and discussed. Our studies show that some kinds of nanomaterials, such as silica nanoparticles and nanosilicates, may be very toxic and even fatal to occupational workers exposed to them without any effective personal protective equipment. More research and collaborative efforts on nanosafety are required in order to prevent and minimize the potential hazards of nanomaterials to humans and the environment.

Yuguo Song

Shichuan Tang

Nanoexposure, Unusual Diseases, and New Health and Safety Concerns

Dendrimers are polybranched and polyfunctionalized tree-like polymers. Unlike linear polymers, they have perfectly defined structure and molecular weight, due to their iterative step-by-step synthesis. Their multivalent structure and supramolecular properties have made them attractive nanotools for applications, particularly in biology and medicine. Among the different biological and medical properties of dendrimers that have been developed over the past decades, the anti-inflammatory properties of several groups of dendrimers are the most recently discovered. Thereof, dendrimers emerge as promising, although heretical, drug candidates for the treatment of still-uncured chronic inflammatory disorders. This mini-review is based on the five main scientific articles giving an overview of what can be the spectrum of anti-inflammatory characteristics displayed by dendrimers.

Myriam Hayder

S&#xE9;verine Fruchon

Jean-Jacques Fourni&#xE9;

Mary Poupot

R&#xE9;my Poupot

Anti-Inflammatory Properties of Dendrimers per se

This study investigated the acute and subchronic inflammatory effects of micrometer-size (micro-size) and nanometer-size (nano-size) particles after intratracheal (i.t.) installation in mice. The role of the type of compound, polymorphism, and size of the particles was investigated. Studied compounds were the two micro-size reference quartzes, SRM1878a and DQ12, a micro- and nano-size rutile titanium dioxide (TiO2), a nano-size anatase, and an amorphous TiO2. Particles were administered by a single i.t. instillation in mice at a fixed dose of 5, 50, and 500 &#x3bc;g, respectively. Inflammation was evaluated from the bronchoalveolar lavage fluid (BALF) content of inflammatory cells, the cytokines tumor necrosis factor alpha (TNF-&#x3b1;) and interleukin 6 (IL-6), as well as from lung histology. Evaluations were at 24 h (acute effects) and 3 months (subchronic effects) after instillations. Both types of quartz induced a dose-dependent acute increase of neutrophils, IL-6, and total protein in BALF. Limited subchronic inflammation was observed. All types of TiO2 induced a dose-dependent acute increase of neutrophils in BALF. In the acute phase, micro- and nano-size rutile and nano-size amorphous TiO2 induced elevated levels of IL-6 and total protein in BALF at the highest dose. At the nano-size rutile and amorphous TiO2, subchronic lung inflammation was apparent from a dose-dependent increase in BALF macrophages. Histology showed little inflammation overall. The two types of quartz showed virtually similar inflammatory effects. Nearly similar effects were observed for two sizes of rutile TiO2. Differences were seen between the different polymorphs of nano-size TiO2, with rutile being the most inflammogenic and amorphous being the most potent in regard to acute tissue damage.

Martin Roursgaard

Keld A. Jensen

Steen S. Poulsen

Niels-Erik V. Jensen

Lars K. Poulsen

Maria Hammer

Gunnar D. Nielsen

Søren T. Larsen

Acute and Subchronic Airway Inflammation after Intratracheal Instillation of Quartz and Titanium Dioxide Agglomerates in Mice

Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanoparticles on pulmonary inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS) as a disease model in innate immunity, and demonstrate that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Second, we introduce the effects of nanoparticles on allergic pulmonary inflammation as a disease model in adaptive immunity, and show that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic inflammation, including adjuvant effects on Th2-milieu. Third, we show that very small nanoparticle exposure exacerbates emphysematous pulmonary inflammation, which is concomitant with enhanced lung expression of proinflammatory molecules (including those that are innate immunity related). Taken together, nanoparticle exposure may synergistically facilitate pathological pulmonary inflammation via both innate and adaptive immunological impairment.

Ken-Ichiro Inoue

Hirohisa Takano

Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

The development of nanoscale molecular probes capable of diagnosis, characterization, and clinical treatment of disease is leading to a new generation of imaging technologies. Such probes are particularly relevant to inflammation, where the detection of subclinical, early disease states could facilitate speedier detection that could yield enhanced, tailored therapies. Nanoparticles offer robust platforms capable of sensitive detection, and early research has indicated their suitability for the detection of vascular activation and cellular recruitment at subclinical levels. This suggests that nanoparticle techniques may provide excellent biomarkers for the diagnosis and progression of inflammatory diseases with magnetic resonance imaging (MRI), fluorescent quantum dots (QDs), and surface enhanced Raman scattering (SERS) probes being just some of the new methodologies employed. Development of these techniques could lead to a range of sensitive probes capable of ultrasensitive, localized detection of inflammation. This article will discuss the merits of each approach, with a general overview to their applicability in inflammatory diseases.

Ross Stevenson

Axel J. Hueber

Alan Hutton

Iain B. McInnes

Duncan Graham

Nanoparticles and Inflammation

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The Scientific World Journal

This Issue is now open for submissions.
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The Scientific World Journal

Nanoparticles and Inflammation

Nanoparticles and Inflammation

Articles

The Inflammatory Process in Response to Nanoparticles

Activation of Neutrophils by Nanoparticles

Nanoexposure, Unusual Diseases, and New Health and Safety Concerns

Anti-Inflammatory Properties of Dendrimers per se

Acute and Subchronic Airway Inflammation after Intratracheal Instillation of Quartz and Titanium Dioxide Agglomerates in Mice

Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

Nanoparticles and Inflammation