Estrogen-mediated impairment of macrophageal uptake of environmental TiO₂particles to explain inflammatory effect of TiO₂on airways during pregnancy

Abstract

Innate defenses against environmental particulate exposures can become deficient when physiological background of the organism is unbalanced. Even those exposures considered innocuous may then become harmful. For example, one of the important inherent risks of pregnancy is increased inflammatory responsiveness in the airways, which extends to exposures considered otherwise innocuous: it has been observed that normally ''inert'' particulates become inflammatory in pregnancy. They lead to enhanced airway inflammation associated with increased asthma risk in the offspring in the BALB/c model. It was hypothesized that pregnancy hormones alter macrophageal uptake and clearance of particles. This study shows that the phagocytic activity of alveolar macrophages (AM) and RAW264.7 cells against titanium dioxide (TiO 2 ) was inhibited in pregnancy by $10% and in vitro by estradiol by $20%; progesterone potentiated this effect. Hence, enhanced inflammation in pregnancy as an outcome of exposure to the ''inert'' TiO 2 may be due to an effect of pregnancy hormones which decrease the ability of the airways to clear the particles. AM (at 10 6 cells/recipient) isogenically transplanted from pregnant mothers into airways of recipients were able to confer the phenotype of inflammatory response to TiO 2 (PMN counts of 1.62 [± 0.19] Â 10 5 /ml versus 0.61 [± 0.13] Â 10 5 /ml in control). Because this small amount of transferred AM could not replace the AM population in the recipients' lungs, it is postulated that the effect is mediated by inhibitory signaling factors that AM produce and release; hence, a list of probable molecules was identified via genome-wide microarray.

Association between Body Powder Use and Ovarian Cancer: The African American Cancer Epidemiology Study (AACES)

“…In this study, elevated estrogen levels during pregnancy were found to contribute to the resulting asthma risk. (20) Our findings also support that enhanced airway inflammation is due to exposure to inert particles. Consistent with a recent study (15) where an association with powder use and asthma was reported, the relationship between body powder use and respiratory conditions likely reflects an enhanced inflammatory response due to powder use, suggesting a mechanism by which EOC risk is increased.…”

“…This finding is also consistent with experimental data showing that in the presence of estrogen and/or estrogen and progesterone, the ability of macrophages to clear inert particulates is altered, enhancing the inflammatory response leading to the development of asthma in mouse offspring. (20) It has also been proposed that chronic inflammation, resulting from exposure to body powder, whether through inhalation or through a transvaginal route, may exert a suppressive effect on adaptive immunity, leading to increased risk of EOC. (30) These findings suggest that AA women may be particularly susceptible to exposure to body powder due to having higher endogenous estrogen levels compared to white women.…”

“…for frequency of use: no exposure, less than daily, daily), adjusting for confounders. Trends were evaluated by statistical tests for the association between frequency/duration/lifetime applications with EOC risk, using Wald tests to simultaneously test the equality of parameter estimates with zero.. Because experimental data suggest a relationship between inhaled inert particles and asthma, (20) a logistic regression analysis was conducted to determine the association between body powder use and upper respiratory conditions (yes, no), controlling for EOC case/control status.…”

“…Experimental data show that the inflammatory response is enhanced in the presence of estrogen and progesterone and we therefore tested for interaction of the association with body powder use by menopausal status. (20) Logistic regression and trend analyses were performed using SAS version 9.4 (Cary, North Carolina).…”

A perspective on the developmental toxicity of inhaled nanoparticles

“…Offspring of mothers exposed to particles developed airway allergy, evidenced by allergic inflammation and airway hyper responsiveness, which was absent in control offspring [131]. The effect of maternal TiO 2 exposure was ascribed to impaired clearance of particles by macrophages and thus a greater inflammatory response in the dams [132]. The latter finding indicates that "inert" particles may become inflammogenic in pregnancy, due to alterations in hormonal balance that subsequently changes regulation of uptake of particles by alveolar macrophages and thus lessens clearance of particles from the maternal lungs.…”