Enhanced Clearance of Silica from Mouse Lung After Instillation of a Leukocyte Chemotactic Factor

Abstract

It has been suggested that increased recruitment of phagocytes and subsequent clearance of particles may follow instillation of a leukocyte chemoattractant to lungs containing silica. The present study quantitated serially the silica content in alveolar spaces, in lung tissue and in hilar lymph nodes of mice that received 2 mg silica only, compared to a group that also received 100 micrograms intratracheal chemotactic factor N-formyl-L-methionyl-leucyl-phenylalanine (FMLP) at 2 and 3 weeks after silica. These mice showed a supplemental increase in alveolar macrophages and neutrophils, and an increase in silica was measured in lavaged cells and fluid soon after FMLP injection. At all times to 16 weeks, the silica content of lung tissue was significantly lower in mice that also received FMLP, and in this group, pulmonary fibrosis was much reduced, as shown morphologically and biochemically. In addition, there was reduced translocation of silica to lymph nodes in FMLP-treated mice. The results indicate that induction of a controlled inflammatory response in the alveoli at a time when particles are present in the pulmonary interstitium can accelerate clearance by increasing phagocyte traffic to the alveoli. The subsequent reduction in particle content of the lung is associated with a lower level of pulmonary fibrosis.

Core-shell silica nanoparticles as fluorescent labels for nanomedicine

“…Although the particle size ͑30 nm diam͒ is too large for excretion through the kidneys and urinary system, 32 the localization of the particles within the mononuclear phagocyte system indicates that the particles may be scavenged and cleared by macrophages consistently with results from pulmonary silica particle exposure. [33][34][35] This possibility is in agreement with our observation that the average dot fluorescence per cell remained relatively constant ͓Fig. 6͑b͔͒.…”

The Concentration of Iron in Real-World Geogenic PM10 Is Associated with Increased Inflammation and Deficits in Lung Function in Mice

“…We have previously shown that community-sampled geogenic PM 10 induces a potent inflammatory response in the lung [9] . This neutrophil dominated response is consistent with many previous studies examining the lung response to inhaled dusts (primarily SiO 2 ) of mineral origin [18] , [26] . While exposure to crystalline silica in mouse models elicits fibrotic changes [27] , [28] , which presumably alters lung function, there appears to be very little data in the literature on the impact of silica on lung function in mouse models (although silicosis in humans is associated with impaired lung function [29] ).…”

“…The 100 µg dose was chosen based on the dose-response data from our previous study [9] as a dose that produces a robust and measurable inflammatory response. This dose (∼5 mg.kg −1 ) is an order of magnitude smaller than typical rodent particle exposure models (∼100 mg.kg −1 [18] ) and is consistent with our prior work on diesel exhaust particles [19] , [20] .…”

“…It should be noted that the exposure doses used in our study (∼5 mg.kg −1 ) are an order of magnitude lower than the doses typically used in mouse studies of pure crystalline silica exposure (e.g. ∼100 mg.kg −1 , [18] ) and silica only constituted a proportion of our particles. These observations suggest that the lung was particularly sensitive to the heterogeneous geogenic particulates used in our study.…”

Critical Role of MARCO in Crystalline Silica–Induced Pulmonary Inflammation

“…The balance between clearance and retention of crystalline silica in the lungs by AM plays an important role in regulating the inflammatory response and silicosis. Previous studies indicate that facilitating the clearance of crystalline silica from the alveolar and interstitial compartments decreases the fibrotic response in the lung (Adamson et al, 1992(Adamson et al, , 1994. Therefore, unsuccessful clearance of crystalline silica may result in persistent inflammation due to prolonged interaction of particles with both immune and non-immune cell populations such as neutrophils, AM, dendritic cells (DCs), and epithelial cells in the lung.…”