Pulmonary Lipid Research Articles

Reexamining the Role of Pulmonary Lipids in the Pathogenesis of Pulmonary Fibrosis.

Pulmonary fibrosis (PF) can be idiopathic or driven by a specific insult, genetic susceptibility, or disease process. Inflammation plays a role in the pathophysiology, the extent of which remains a longstanding topic of debate. More recently, there has been increasing interest in a potential inciting role for aberrant lipid metabolism. Lipids are essential for the structure and function of all cell membranes, but specifically in the lung for surfactant composition, intra- and intercellular lipid mediators, and lipofibroblasts. Clinically, there is evidence of increased lipid deposition in the subpleural space and at a whole-lung tissue level in PF. There is evidence of increased parenchymal lipid deposition and abnormal mediastinal fat shape on chest computed tomography. A protective role for cholesterol-lowering drugs, including statins and ezetimibe, has been described in PF. At a cellular level, fatty acid, phospholipid, and glucose metabolism are disordered, as is the production of lipid mediators. Here we put forward the argument that there is substantive clinical and biological evidence to support a role for aberrant lipid metabolism and lipid mediators in the pathogenesis of PF.

The Effect of Chlorogenic Acid on Methotrexate-Induced Oxidative Stress and Inflammation in Lung Tissue of Rats

Although methotrexate (MTX) is a widely used chemotherapeutic agent, lung toxicity remains a significant problem, limiting its use. The molecular mechanism of MTX-related lung toxicity is not fully understood. However, increased reactive oxygen species (ROS)-induced oxidative stress (OS) and inflammation play an important role in lung injury. Chlorogenic acid (CHA) is a natural phenolic compound that has been shown in recent years to have beneficial effects in many pathologies associated with OS and inflammation. This study focused on investigating for the first time, the potential therapeutic effects of CHA in the lung tissue of rats exposed to MTX. After lung toxicity was induced in rats by MTX (20 mg/kg) injection on the first day, two different doses of CHA (1.5 and 3 mg/kg) were used for treatment for 3 days. The results showed that CHA treatment reduced the level of pulmonary lipid peroxidation, inflammation, and apoptosis and promoted the pulmonary antioxidant system in rats subjected to MTX. Taken together, the antioxidant and anti-inflammatory properties of CHA may play a central role in attenuating MTX-induced lung injury, but the exact mechanism needs to be investigated in more extensive preclinical studies.

Sex-specific alterations in pulmonary metabolic, xenobiotic and lipid signalling pathways after e-cigarette aerosol exposure during adolescence in mice

BackgroundE-cigarette use is now prevalent among adolescents and young adults, raising concerns over potential adverse long-term health effects. Although it is hypothesised that e-cigarettes promote inflammation, studies have yielded conflicting...

Investigating the effects of dexamethasone on pulmonary surfactant lipids based on lipidomics studies.

Dexamethasone, a glucocorticoid commonly used in pediatric patients, has potent anti-inflammatory and immunosuppressive properties. However, it is associated with side effects such as reduced lung function and decreased immunity. Pulmonary surfactant lipids are closely linked to lung disease and play a role in reducing surface tension, immune response and antiviral activity. The dysregulation of lipid metabolism is closely associated with lung disease. Hence, untargeted lipidomics may be instrumental in elucidating the effects of dexamethasone on pulmonary surfactant lipids. We obtained surfactant lipid samples from the bronchoalveolar lavage fluid of young mice injected subcutaneously with dexamethasone and conducted a comprehensive lipidomic analysis, comparing them with a control group. We observed a decrease in lipids, such as phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine, and an increase in ceramide, fatty acid, diacylglycerol and monoglyceride, which may impact lung health. This study revealed the influence of dexamethasone on pulmonary surfactant lipids, offering new insights into adverse reactions in clinical settings.

Fagopyrum Dibotrys Rhizoma regulates pulmonary lipid metabolic homeostasis and the ERK-cPLA2 pathway to alleviate asthma in mice

BackgroundAsthma is a complex disease with mechanisms involving multiple factors, and there is still a lack of highly effective and low-side-effect drugs. Traditional Chinese medicine Fagopyrum Dibotrys Rhizoma (FDR) has been applied for the treatment of acute and chronic bronchitis as well as bronchial asthma due to its favorable pharmacological activity. However, the exact mechanism of FDR remains unclear. ObjectiveA mouse model of asthma was created using OVA and HDM. To investigate the mechanism of FDR in asthma treatment, a combination of network pharmacology, lipidomics, and molecular biology approaches was employed. MethodsTo evaluate the therapeutic effects of FDR on asthma, we established two distinct models of asthma in C57BL/6 J mice using OVA and HDM, respectively. We then employed LC-MS to analyze the major chemical constituents in FDR. Next, the network pharmacology approach was used to predict the potential targets and mechanisms of FDR in asthma treatment. Additionally, lipidomics analysis of mouse serum was conducted using LC-MS. Finally, the impact of FDR on the ERK -cPLA2 signaling pathway was investigated through Western Blotting assay. ResultsFDR treatment has been shown to improve histomorphological changes, lung function and inflammation in models of OVA and HDM-induced asthma. Using UPLC/LTQ-Orbitrap-MS, we were able to identify 12 potential active components. Network pharmacology analysis revealed that FDR shares 75 targets with asthma. Further analysis using GO and KEGG pathways demonstrated the involvement of key pathways such as PI3K-Akt, TNF, and MAPK. Additionally, lipidomics analysis of the serum from OVA and HDM induced asthma mice showed disturbances in lipid metabolism, which were effectively ameliorated by FDR treatment. Mechanistically, FDR inhibits ERK1/2-cPLA2, leading to a reduction in lysophospholipids and restoration of lipid balance, thereby aiding in the treatment of asthma. ConclusionFDR has been shown to improve lipid metabolism disorder in the serum of asthmatic mice, thereby potentially serving as a treatment for asthma. This can be achieved by regulating the activation levels of ERK1/2 and p38MAPK. Consequently, the production of lysophosphatide is reduced, thereby alleviating the disorder of lipid metabolism and achieving the desired therapeutic effect in asthma treatment.

A comparative study on the protective effects of cuminaldehyde, thymoquinone, and gallic acid against carbon tetrachloride-induced pulmonary and renal toxicity in rats by affecting ROS and NF-κB signaling

CCl4 toxicity is a fatal condition that can cause numerous organ dysfunctions. We evaluated and compared the protective effects of cuminaldehyde (CuA), thymoquinone (TQ), and gallic acid (GA) on CCl4-induced pulmonary and renal toxicity in rats. The impacts of these compounds on CCl4-induced oxidative stress, inflammation, and morphological alterations were examined. The results showed that the compounds under investigation prevented CCl4 from significantly increasing pulmonary and renal lipid peroxidation and NO levels, as well as massively depleting GSH levels and GPX and SOD activities. Moreover, they suppressed the CCl4-induced increase in mucus secretion in the lung and upregulated the gene expression of pulmonary and renal NF-ҡB, iNOS, TNF-α, and COX-2. The heatmap cluster plots showed that GA and TQ had better protective potencies than CuA. The external organ morphology, histopathological results, and chest X-ray analysis confirmed the toxicity of CCl4 and the protective influences of the tested compounds in both the lungs and kidneys of rats. These compounds displayed predicted competitive inhibitory effects on iNOS activity and may block the IL-13α2 receptor, as revealed by molecular docking analysis. Thus, CuA, TQ, and GA, particularly the latter two, are prospective protective compounds against the pulmonary and renal toxicity caused by CCl4.

Untargeted lipidomics of bronchopulmonary dysplasia induced by hyperoxia exposure in rats.

Bronchopulmonary dysplasia (BPD), characterized by impaired lung development, remains a leading cause of morbidity and mortality in premature infants. The synthesis and metabolism of lipids play a critical role in normal lung development, such as dipalmitoylphosphatidylcholine, a key component of pulmonary surfactant (PS). Therefore, we conducted a lipidomics study of rat lung tissue to explore the changes of pulmonary lipid composition in the progression of BPD disease. In this study, we exposed neonatal Sprague-Dawley (SD) rats to hyperoxia for 14 days. After hyperoxia exposure, the lung tissues of rats were analyzed pathologically, and untargeted lipidomics was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hematoxylin-eosin (H&E) staining showed that the alveoli enlarged, the number of alveoli decreased and the pulmonary surfactant-associated protein D (SFTPD) decreased in hyperoxia-exposed rats. A total of 620 pulmonary lipids were detected by LC-MS/MS, covering 27 lipid categories. The most common lipids were triacylglycerol (TAG), followed by phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Compared with those rats exposed to normoxic conditions, the lipid levels in the lungs of rats exposed to hyperoxia for 14 days generally decreased, with the levels of TAG and PC decreasing most significantly. In short, our results provide a clue for finding therapeutic targets and biomarkers of a BPD rat model lung liposome.

Docosahexaenoic Acid Controls Pulmonary Macrophage Lipid Raft Size and Inflammation

BackgroundDocosahexaenoic acid (DHA) controls the biophysical organization of plasma membrane sphingolipid/cholesterol-enriched lipid rafts to exert anti-inflammatory effects, particularly in lymphocytes. However, the impact of DHA on the spatial arrangement of alveolar macrophage lipid rafts and inflammation is unknown. ObjectivesThe primary objective was to determine how DHA controls lipid raft organization and function of alveolar macrophages. As proof-of-concept, we also investigated DHA’s anti-inflammatory effects on select pulmonary inflammatory markers with a murine influenza model. MethodsMH-S cells, an alveolar macrophage line, were treated with 50 μM DHA or vehicle control and were used to study plasma membrane molecular organization with fluorescence-based methods. Biomimetic membranes and coarse grain molecular dynamic (MD) simulations were employed to investigate how DHA mechanistically controls lipid raft size. qRT-PCR, mass spectrometry, and ELISAs were used to quantify downstream inflammatory signaling transcripts, oxylipins, and cytokines, respectively. Lungs from DHA-fed influenza-infected mice were analyzed for specific inflammatory markers. ResultsDHA increased the size of lipid rafts while decreasing the molecular packing of the MH-S plasma membrane. Adding a DHA-containing phospholipid to a biomimetic lipid raft-containing membrane led to condensing, which was reversed with the removal of cholesterol. MD simulations revealed DHA nucleated lipid rafts by driving cholesterol and sphingomyelin into rafts. Downstream of the plasma membrane, DHA lowered the concentration of select inflammatory transcripts, oxylipins, and IL-6 secretion. DHA lowered pulmonary Il6 and Tnf-α mRNA expression and increased anti-inflammatory oxylipins of influenza-infected mice. ConclusionsThe data suggest a model in which the localization of DHA acyl chains to nonrafts is driving sphingomyelin and cholesterol molecules into larger lipid rafts, which may serve as a trigger to impede signaling and lower inflammation. These findings also identify alveolar macrophages as a target of DHA and underscore the anti-inflammatory properties of DHA for lung inflammation.

Hibifolin protected pro-inflammatory response and oxidative stress in LPS-induced acute lung injury through antioxidative enzymes and the AMPK2/Nrf-2 pathway.

ALI is a grave medical ailment that manifests as abrupt inflammation of the lungs and diminished oxygen levels. It poses a considerable challenge to the medical fraternity, with elevated rates of morbidity and mortality. Our research endeavors to investigate the potential of hibifolin, a flavonoid glucuronide, imbued with potent antioxidant properties, and its molecular mechanism to combat LPS-induced ALI in mice. The study utilized ICR mice to create an ALI model induced by LPS. Prior to LPS administration, hibifolin was given at 10, 30, or 50 mg/kg, or dexamethasone was given at 1 mg/kg to assess its preventative impact. Changes in lung tissue, pulmonary edema, and lipid peroxidation were analyzed using H&E stain assay, lung wet/dry ratio assay, and MDA formation assay, respectively. Activity assay kits were used to measure MPO activity and antioxidative enzymes (SOD, CAT, GPx) activity in the lungs. Western blot assay was used to determine the phosphorylation of Nrf-2 and AMPK2 in the lungs. Hibifolin demonstrated a concentration-dependent improvement in LPS-induced histopathologic pulmonary changes. This treatment notably mitigated pulmonary edema, lipid peroxidation, and MPO activity in ALI mice. Additionally, hibifolin successfully restored antioxidative enzyme activity in the lungs of ALI mice. Moreover, hibifolin effectively promoted Nrf-2 phosphorylation and reinstated AMPK2 phosphorylation in the lungs of ALI mice. The results indicate that hibifolin could effectively alleviate the pathophysiological impact of LPS-induced ALI. This is likely due to its antioxidative properties, which help to restore antioxidative enzyme activity and activate the AMPK2/Nrf2 pathway. These findings are valuable in terms of enhancing our knowledge of ALI treatment and pave the way for further investigation into hibifolin as a potential therapeutic option for lung injuries.

Structural changes in layers of lipid mixtures at low surface tensions

Layers of pulmonary lipids on an aqueous substrate at non-equilibrium conditions can decrease the surface tension of water to quite low values. This is connected with different relaxation processes occurring at the interface and the associated changes in the surface layer structure. Results of measurements by the combination of methods like surface rheology, ellipsometry, Brewster angle microscopy, and IRRAS for spread layers of lipid mixtures open a possibility to specify the dynamics of structural changes at conditions close to the physiological state. At sufficiently low surface tension values (below 5 mN/m) significant changes in the ellipsometric signal were observed for pure DPPC layers, which can be related to a transition from 2D to 3D structures caused by the layer folding. The addition of other lipids can accelerate the relaxation processes connected with squeezing-out of molecules or multilayer stacks formation hampering thereby a decrease of surface tension down to low values corresponding to the folding of the monolayer.

Albumin Proteins as Delivery Vehicles for PFAS Contaminants into Respiratory Membranes.

Poly- and perfluoroalkyl substances (PFAS) are a family of chemicals that have been used in a wide range of commercial products. While their use is declining, the prevalence of PFAS, combined with their chemical longevity, ensures that detectable levels will remain in the environment for years to come. As such, there is a pressing need to understand how PFAS contaminants interact with other elements of the human exposome and the consequences of these interactions for human health. Using serum albumin as a model system, we show that proteins can bind PFAS contaminants and facilitate their incorporation into model pulmonary surfactant systems and lipid bilayers. Protein-mediated PFAS delivery significantly altered the structure and function of both model membrane systems, potentially contributing to respiratory dysfunction and airway diseases in vivo. These results provide valuable insights into the synergistic interaction between PFAS contaminants and other elements of the human exposome and their potential consequences for human health.

HLA-DRB1*14:54 Is Associated with Pulmonary Alveolar Proteinosis: A Retrospective Real-World Audit.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterized by abnormal accumulation of pulmonary surfactant lipids in alveoli or terminal bronchioles, leading to increased infection risk and progressive respiratory failure. Approximately more than 90% of all cases are autoimmune PAP (aPAP). Since one of the predisposing factors has been identified as genes located within the major-histocompatibility-complex region, an investigation of human leukocyte antigen (HLA) alleles associated with the risk of aPAP is warranted. We retrospectively studied 60 patients pathologically diagnosed with PAP from 2019 to 2022. Patients were divided into the aPAP group or secondary PAP (sPAP) group according to their clinical information. Qualified DNA was extracted from the paraffin-embedded tissue of 28 patients, and the PCR-sequence-based typing method was used for HLA-DRB1 genotyping. A similar HLA-DRB1 allele profile (including the HLA-DRB1*08:03) between the aPAP group and sPAP group was revealed, except that HLA-DRB1*14:54, which has never been reported in aPAP patients, was only detected in the aPAP group rather than the sPAP group (19.4% vs. 0.0%, p = 0.030). Under inhaled granulocyte-macrophage colony-stimulating factor therapy, more clinical remission was observed in HLA-DRB1*14:54 carriers rather than in HLA-DRB1*08:03 carriers (80.0% vs. 57.1%). Our real-world study revealed for the first time that a population with HLA-DRB1*14:54 was subject to aPAP, and HLA-DRB1*14:54 might imply a response in aPAP patients to inhaled granulocyte-macrophage colony-stimulating factor in aPAP patients.

Dynamic Properties of Pulmonary Lipid Monolayers on the Surfaces of Sodium Polystyrene Sulfonate and Polydiallyldimethylammonium Chloride Solutions

Dynamic Properties of Pulmonary Lipid Monolayers on the Surfaces of Sodium Polystyrene Sulfonate and Polydiallyldimethylammonium Chloride Solutions

Modulation of cigarette smoke induced alterations by aqueous Ocimum sanctum leaf extract in pulmonary tissue of rodents

Smoking has been associated with an increased risk of asthma, lung cancer, cardiovascular diseases, chronic bronchitis, and a massive amount of oxidative stress. The present study was undertaken to determine the modulatory effects of Holi Basil/Tulsi, (Ocimum sanctum) leaf extract on cigarette smoke-induced pulmonary damage in mice. Cigarette smoke (CS) inhalation increased the levels of pulmonary lipid peroxidation, and reactive oxygen species and decreased the levels of glutathione. Histoarchitectural alterations and enhanced tissue lactate dehydrogenase (LDH) activity in pulmonary tissue was distinctly indicative of damage. Enhanced mucin production was also observed through mucicarmine and Alcian Blue-Periodic Acid Schiff (PAS) staining. Increased expression of MUC5AC was also observed. Alterations in the lung were also evident through FTIR studies. Administration of Ocimum sanctum leaf extract (80 mg/kg b.w) to CS exposed mice ameliorated these alterations to a greater extent. These findings are suggestive of the fact that Ocimum sanctum leaf extract effectively modulated CS-induced deleterious effects on pulmonary tissue.

Dynamic Properties of Pulmonary Lipid Monolayers on the Surfaces of Sodium Polystyrene Sulfonate and Polydiallyldimethylammonium Chloride Solutions

Pulmonary surfactant, which is a complex mixture of lipids and proteins, plays a key role in the functional properties of the respiratory system. Lipids form complexes with proteins to maintain low values of surface tension at continuous compression/expansion deformations. However, interactions that lead to the complexation still remain to be unknown thus significantly hampering the development of synthetic analogs of the natural pulmonary surfactant. In this work, the methods of surface rheology and ellipsometry have been employed to study the dynamic properties of model phospholipid monolayers applied onto the surfaces of synthetic polyelectrolyte solutions. It has been shown, that electrostatic or hydrophobic interactions between lipids and macromolecules are insufficient for the efficient complexation and maintenance of low surface tension values.

Analysis of tissue lipidomics and computed tomography pulmonary fat attenuation volume (CTPFAV ) in idiopathic pulmonary fibrosis.

There is increasing interest in the role of lipids in processes that modulate lung fibrosis with evidence of lipid deposition in idiopathic pulmonary fibrosis (IPF) histological specimens. The aim of this study was to identify measurable markers of pulmonary lipid that may have utility as IPF biomarkers. IPF and control lung biopsy specimens were analysed using a unbiased lipidomic approach. Pulmonary fat attenuation volume (PFAV) was assessed on chest CT images (CTPFAV ) with 3D semi-automated lung density software. Aerated lung was semi-automatically segmented and CTPFAV calculated using a Hounsfield-unit (-40 to -200HU) threshold range expressed as a percentage of total lung volume. CTPFAV was compared to pulmonary function, serum lipids and qualitative CT fibrosis scores. There was a significant increase in total lipid content on histological analysis of IPF lung tissue (23.16 nmol/mg) compared to controls (18.66 mol/mg, p = 0.0317). The median CTPFAV in IPF was higher than controls (1.34% vs. 0.72%, p < 0.001) and CTPFAV correlated significantly with DLCO% predicted (R2 = 0.356, p < 0.0001) and FVC% predicted (R2 = 0.407, p < 0.0001) in patients with IPF. CTPFAV correlated with CT features of fibrosis; higher CTPFAV was associated with >10% reticulation (1.6% vs. 0.94%, p = 0.0017) and >10% honeycombing (1.87% vs. 1.12%, p = 0.0003). CTPFAV showed no correlation with serum lipids. CTPFAV is an easily quantifiable non-invasive measure of pulmonary lipids. In this pilot study, CTPFAV correlates with pulmonary function and radiological features of IPF and could function as a potential biomarker for IPF disease severity assessment.

Occupational exposure of vehicular emissions and cardiorespiratory risk among urban metropolitan bus drivers: A cross-sectional comparative study.

Vehicular emissions on long-term exposure predispose metropolitan bus drivers to cardiorespiratory ailments. To evaluate the cardiorespiratory risk of urban metropolitan bus drivers related to vehicular emission exposure. Bus drivers (with service >5 years, n = 254) and their administrative controls (primarily engaged in indoor white collared jobs, n = 73) were recruited. Demographic, occupational and clinical details were collected through pre-validated standardized format. Pulmonary Function Test (PFT) and lipid profile were carried out with standard protocol. Risk for cardiovascular events for preceding 10-years was estimated with WHO/ISH risk prediction chart and QRISK3 score. Exposure assessments for particulate matter (PM) were performed for both groups while duty hours. Exposure of drivers to PM2.5 six times and PM10 five times higher in comparison to administration staff (PM2.5- 970.9 v/s 145.0μg/m3 TWA and PM10- 1111.7 v/s 233.8μg/m3 TWA). Bus drivers exhibited significantly higher prevalence of respiratory symptoms (dyspnea-25% v/s 6.8% and cough-20.1% v/s 9.8%) and compromised PFT (obstructive-21% v/s 5.7% and restrictive-4.2% v/s 2.9%) in comparison to controls. Multivariate regression statistics reveal a significant decline for FEV1/FVC and FEV25-75% among bus drivers compared to controls, controlling the influence of physiological and environmental factors. The difference between predicted cardiac age and their respective chronological age was twice higher (8.3 v/s 4.3 years) among drivers compared to their administration staff. Bus drivers were exposed to high levels of outdoor air pollutants. Further, the drivers exhibited higher risk for ischemic attack and obstructive airway diseases as compared to administration staff.

Effect of budesonide formoterol combined with tiotropium bromide on pulmonary function and inflammatory factors in patients with asthma-COPD overlap syndrome.

To investigate the clinical efficacy of combining budesonide formoterol with tiotropium bromide for treating asthma-chronic obstructive pulmonary disease overlap syndrome (AOCS). The data of 104 patients with AOCS admitted to our hospital from December 2019 to December 2020 were assessed, randomly and divided into an experimental group (comprising 52 patients, receiving drug combination therapy) and a conventional group (comprising 52 patients, receiving drug therapy alone). Patients' clinical efficacy, pulmonary function, fractioned exhaled nitric oxide (FeNO), immune function, endothelial function, serum lipid peroxidation injury indexes, adverse reactions, and quality of life scores were compared. Prior to treatment, no significant differences were observed in various pulmonary function indicators, FeNO, immune function, endothelial function, and lipid peroxidation injury indexes between the two groups (P > 0.05). However, after treatment, all observation indexes in both groups improved to different levels, with the experimental group -demonstrating -significantly superior improvement, compared to the conventional group (P < 0.05). We also observed that adverse reactions in the experimental group were significantly lower than in the conventional group (P < 0.05). The combination of budesonide formoterol to tiotropium bromide in treating asthma-COPD overlap syndrome may significantly improve pulmonary function, endothelial function, and immune status of patients and encourage the recovery of serum lipid peroxidation injury; therefore, this may deserve widespread adoption and application.

Lipid mediators in the regulation of innate and adaptive immunity.

Lipid mediators in the regulation of innate and adaptive immunity.

Role of PPARγ in dyslipidemia and altered pulmonary functioning in mice following ozone exposure.

Exposure to ozone causes decrements in pulmonary function, a response associated with alterations in lung lipids. Pulmonary lipid homeostasis is dependent on the activity of peroxisome proliferator activated receptor gamma (PPARγ), a nuclear receptor that regulates lipid uptake and catabolism by alveolar macrophages (AMs). Herein, we assessed the role of PPARγ in ozone-induced dyslipidemia and aberrant lung function in mice. Exposure of mice to ozone (0.8 ppm, 3 h) resulted in a significant reduction in lung hysteresivity at 72 h post exposure; this correlated with increases in levels of total phospholipids, specifically cholesteryl esters, ceramides, phosphatidylcholines, phosphorylethanolamines, sphingomyelins, and di- and triacylglycerols in lung lining fluid. This was accompanied by a reduction in relative surfactant protein-B (SP-B) content, consistent with surfactant dysfunction. Administration of the PPARγ agonist, rosiglitazone (5 mg/kg/day, i.p.) reduced total lung lipids, increased relative amounts of SP-B, and normalized pulmonary function in ozone-exposed mice. This was associated with increases in lung macrophage expression of CD36, a scavenger receptor important in lipid uptake and a transcriptional target of PPARγ. These findings highlight the role of alveolar lipids as regulators of surfactant activity and pulmonary function following ozone exposure and suggest that targeting lipid uptake by lung macrophages may be an efficacious approach for treating altered respiratory mechanics.