Anin vitrostudy of the effect of size and timing of administration of titanium dioxide particles on antigen presenting activity of alveolar macrophages and peripheral blood monocytes

Abstract

Previous studies have shown that inhaled particles exacerbate asthma and allergic rhinitis. Several factors related to the particle may play a role in immune-stimulating activity; however, the underlying mechanisms remain unclear. We carried out in vitro studies to investigate the effects of TiO(2) particle exposure on antigen presenting activity and expression of the associated cell-surface molecules (Ia, B7.1, B7.2) in rat derived monocytes and alveolar macrophages, in terms of two aspects of the particles: (1) size (59 nm (ST) and 350 nm (LT) particles), and (2) the timing of particle exposure (before antigen exposure or co-administered). Results indicated that particle exposure prior to antigen exposure led to decreased antigen presenting activity in both types of cell. This decrease was greater with ST particles. In monocytes, the expression of cell surface molecules decreased similarly with both particles. Conversely, alveolar macrophages showed greater expression of Ia with ST than with LT exposures. Ia expression was confirmed to be functionally active by a mixed lymphocyte reaction. It is possible that particle exposure might result in poor antigen processing, thereby leading to decreased antigen presenting activity. Co-exposure of particles and antigen induced an increase in antigen presenting activity with both types of particle; however, ST exposure induced greater antigen presenting activity. The expression of Ia also increased similarly with both particle sizes. This suggests that, in a co-exposure situation, antigen may be processed without intensive retardation by particles, and factors other than Ia may affect antigen presenting activity. In conclusion, both size and timing of exposure to TiO(2) particles affect antigen presenting activity of monocytes and alveolar macrophages.

Toxicity of Titanate Nanosheets on Human Immune Cells

“…Several in vitro studies also provide further information regarding the direct effects of TiO 2 nanoparticles on immune cells. Munidasa et al reported that TiO 2 nanoparticles showed greater influence on the antigen presenting activity of monocytes and alveolar macrophages [30]. In addition, Moon et al showed a reduction in lymphocyte proliferation induced by lipopolysaccharide (LPS) or concanavalin A (Con A) upon exposure to TiO 2 nanoparticles [29].…”

Metal Nanomaterials: Immune Effects and Implications of Physicochemical Properties on Sensitization, Elicitation, and Augmentation of Allergic Disease

“…The degree of activation has been further correlated to properties including size, surface modification, crystallinity, and morphology (527,538,1042,1050,1051). Several studies have also reported increases in many of the same markers on DC isolated from animals exposed to metal nanomaterials in vivo (773,844,1052).…”

“…Some metal nanomaterials have been shown to enhance antigen-presenting behaviors of pulmonary macrophages, an effect which could also promote sensitization by generating an additional population of cells capable of stimulating adaptive immune cells. FeNP and TiO2NP have been shown to increase expression levels of several activation markers by pulmonary macrophages that indicate enhanced antigen presenting capacity (773,844). Several metal nanomaterials have also been shown to alter macrophage chemotactic ability, which may further impact their potential to act as APC in the lungs (845).…”

“…Likewise, metal nanomaterials capable of enhancing GM-CSF production in the lungs, dependently or independently of TLR-4 signaling modulation, may promote sensitization by increasing the number of potential APC in the airways. TiO2NP, QD, and ZnONP have been shown to increase surface expression of CD11c, CD80, CD86, and MHC II by pulmonary macrophages, as well as enhance their antigen presenting capacity in vitro (773,(867)(868)(869).…”