ABSTRACT
Rheumatoid arthritis (RA) is characterized by extra-articular involvement including lung disease, yet the mechanisms linking the two conditions are poorly understood. The collagen-induced arthritis (CIA) model was combined with the organic dust extract (ODE) airway inflammatory model to assess bone/joint-lung inflammatory outcomes. DBA/1J mice were intranasally treated with saline or ODE daily for 5 weeks. CIA was induced on days 1 and 21. Treatment groups included sham (saline injection/saline inhalation), CIA (CIA/saline), ODE (saline/ODE), and CIA + ODE (CIA/ODE). Arthritis inflammatory scores, bones, bronchoalveolar lavage fluid, lung tissues, and serum were assessed. In DBA/1J male mice, arthritis was increased in CIA + ODE > CIA > ODE versus sham. Micro-computed tomography (µCT) demonstrated that loss of BMD and volume and deterioration of bone microarchitecture was greatest in CIA + ODE. However, ODE-induced airway neutrophil influx and inflammatory cytokine/chemokine levels in lavage fluids were increased in ODE > CIA + ODE versus sham. Activated lung CD11c+ CD11b+ macrophages were increased in ODE > CIA + ODE > CIA pattern, whereas lung hyaluronan, fibronectin, and amphiregulin levels were greatest in CIA + ODE. Serum autoantibody and inflammatory marker concentrations varied among experimental groups. Compared with male mice, female mice showed less articular and pulmonary disease. The interaction of inhalation-induced airway inflammation and arthritis induction resulted in compartmentalized responses with the greatest degree of arthritis and bone loss in male mice with combined exposures. Data also support suppression of the lung inflammatory response, but increases in extracellular matrix protein deposition/interstitial disease in the setting of arthritis. This coexposure model could be exploited to better understand and treat RA-lung disease. © 2019 American Society for Bone and Mineral Research.
Subject(s)
Arthritis, Experimental/complications , Arthritis, Rheumatoid/complications , Dust , Inflammation/complications , Lung Diseases/etiology , Lung/pathology , Animals , Arthritis, Experimental/blood , Arthritis, Experimental/pathology , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/pathology , Autoantibodies/blood , Biomarkers/blood , Cancellous Bone/pathology , Collagen , Extracellular Matrix Proteins/metabolism , Female , Inflammation/blood , Inflammation/pathology , Joints/pathology , Lung Diseases/blood , Lung Diseases/pathology , Male , Mice , Staining and LabelingABSTRACT
Skeletal health consequences associated with inflammatory diseases of the airways significantly contribute to morbidity. Sex differences have been described independently for lung and bone diseases. Repetitive inhalant exposure to lipopolysaccharide (LPS) induces bone loss and deterioration in male mice, but comparison effects in females are unknown. Using an intranasal inhalation exposure model, 8-week-old C57BL/6 male and female mice were treated daily with LPS (100 ng) or saline for 3 weeks. Bronchoalveolar lavage fluids, lung tissues, tibias, bone marrow cells, and blood were collected. LPS-induced airway neutrophil influx, interleukin (IL)-6 and neutrophil chemoattractant levels, and bronchiolar inflammation were exaggerated in male animals as compared to female mice. Trabecular bone micro-CT imaging and analysis of the proximal tibia were conducted. Inhalant LPS exposures lead to deterioration of bone quality only in male mice (not females) marked by decreased bone mineral density, bone volume/tissue volume ratio, trabecular thickness and number, and increased bone surface-to-bone volume ratio. Serum pentraxin-2 levels were modulated by sex differences and LPS exposure. In proof-of-concept studies, ovarectomized female mice demonstrated LPS-induced bone deterioration, and estradiol supplementation of ovarectomized female mice and control male mice protected against LPS-induced bone deterioration findings. Collectively, sex-specific differences exist in LPS-induced airway inflammatory consequences with significant differences found in bone quantity and quality parameters. Male mice demonstrated susceptibility to bone loss and female animals were protected, which was modulated by estrogen. Therefore, sex differences influence the biologic response in the lung-bone inflammatory axis in response to inhalant LPS exposures.
Subject(s)
Bone Resorption/immunology , Bone and Bones/immunology , Hormone Replacement Therapy , Inflammation/immunology , Lung/immunology , Animals , Bone Resorption/drug therapy , Estradiol/therapeutic use , Female , Inflammation/drug therapy , Inhalation Exposure , Male , Mice , Mice, Inbred C57BL , Ovariectomy , Sex , Tomography, X-Ray ComputedABSTRACT
Laser-induced fluorescence (LIF) techniques to analyze atmospheric aerosols are commonly applied for research and human exposure monitoring, but are very expensive or offer poor spectral resolution. Here, we discuss how a recently proposed instrument can acquire resolved fluorescence spectra from many individual particles in a single camera image using four excitation wavelengths matched with common biological fluorophores for particle discrimination at lower cost. We discuss emission intensity calibration and demonstrate spectral differentiation among four species of pollen. These data provide context for how the instrument could be developed for pollen and mold-spore detection or for use by citizen scientists.