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Lung macrophages constitute a sophisticated surveillance and defense system that contributes to tissue homeostasis and host defense and allows the host to cope with the myriad of insults and antigens to which the lung mucosa is exposed. As opposed to alveolar macrophages, lung interstitial macrophages (IMs) express high levels of Type 2 major histocompatibility complex (MHC-II), a hallmark of antigen-presenting cells. Here, we showed that lung IMs, like dendritic cells, possess the machinery to present soluble antigens in an MHC-II-restricted way. Using ex vivo ovalbumin (OVA)-specific T cell proliferation assays, we found that OVA-pulsed IMs could trigger OVA-specific CD4 + T cell proliferation and Foxp3 expression through MHC-II-, IL-10-, and transforming growth factor β-dependent mechanisms. Moreover, we showed that IMs efficiently captured locally instilled antigens in vivo , did not migrate to the draining lymph nodes, and enhanced local interactions with CD4 + T cells in a model of OVA-induced allergic asthma. These results support that IMs can present antigens to CD4 + T cells and trigger regulatory T cells, which might attenuate lung immune responses and have functional consequences for lung immunity and T cell-mediated disorders.

Alveolar macrophages (AMs) are functionally important innate cells involved in lung homeostasis and immunity and whose diversity in health and disease is a subject of intense investigations. Yet, it remains unclear to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Here, we aimed to explore heterogeneity of human AMs isolated from healthy nonsmokers, smokers without COPD, and smokers with COPD by analyzing BAL fluid cells by flow cytometry and bulk and single-cell RNA sequencing. We found that subpopulations of BAL fluid CD206 + macrophages could be distinguished based on their degree of autofluorescence in each subject analyzed. CD206 + autofluorescent high AMs were identified as classical, self-proliferative AM, whereas autofluorescent low AMs were expressing both monocyte and classical AM-related genes, supportive of a monocytic origin. Of note, monocyte-derived autofluorescent low AMs exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine IL-10. Interestingly, single-cell RNA-sequencing analyses showed that transcriptionally distinct clusters of classical and monocyte-derived AM were uniquely enriched in smokers with and without COPD as compared with healthy nonsmokers. Of note, such smoking-associated clusters exhibited gene signatures enriched in detoxification, oxidative stress, and proinflammatory responses. Our study independently confirms previous reports supporting that monocyte-derived macrophages coexist with classical AM in the airways of healthy subjects and patients with COPD and identifies smoking-associated changes in the AM compartment that may favor COPD initiation or progression.

Myoferlin, an emerging oncoprotein, has been associated with a low survival in several cancer types including pancreas ductal adenocarcinoma where it controls mitochondria structure and respiratory functions. Owing to the high susceptibility of KRAS-mutated cancer cells to iron-dependent cell death, ferroptosis, and to the high iron content in mitochondria, we investigated the relation existing between mitochondrial integrity and iron-dependent cell death. We discovered that myoferlin targeting with WJ460 pharmacological compound triggered mitophagy and ROS accumulation culminating with lipid peroxidation and apoptosis-independent cell death. WJ460 caused a reduction of the abundance of ferroptosis core regulators x c - cystine/glutamate transporter and GPX-4. Mitophagy inhibitor Mdivi1 and iron chelators inhibited the myoferlin-related ROS production and restored cell growth. Additionally, we reported a synergic effect between ferroptosis inducers, erastin and RSL3, and WJ460., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Position-specific isotope analysis by Nuclear Magnetic Resonance spectrometry was employed to study the 13 C intramolecular isotopic fractionation associated with the migration of organic substrates through different stationary phases chromatography columns. Liquid chromatography is often used to isolate compounds prior to their isotope analysis and this purification step potentially alters the isotopic composition of target compounds introducing a bias in the later measured data. Moreover, results from liquid chromatography can yield the sorption parameters needed in reactive transport models that predict the transport and fate of organic contaminants to in the environment. The aim of this study was to use intramolecular isotope analysis to study both 13 C and 15 N isotope effects associated with the elution of paracetamol (acetaminophen) through different stationary phases and to compare them to effects observed previously for vanillin. Results showed very different intramolecular isotope fractionation profiles depending on the chemical structure of the stationary phase. The data also demonstrate that both the amplitude and the distribution of measured isotope effects depend on the nature of the non-covalent interactions involved in the migration process. Results provided by theoretical calculation performed during this study also confirmed the direct link between observed intramolecular isotope fractionation and the nature of involved intermolecular interactions. It is concluded that the nature of the stationary phase through which the substrate passes has a major impact on the intramolecular isotopic composition of organic compounds isolated by chromatography methods.., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Soil thin-layer chromatography with water or water-methanol as solvents allows observation and measurement of the mobility of labelled pesticides through soil microstructures. Eleven different sieved matrices were studied: pure humine, pure clays, schists and soils. Ionized compounds (paraquat, glyphosate) were tightly bound to these matrices. The other compounds, lipophilic and generally non-ionized ones, migrated in the same order on most of the studied matrices, either mineral or organic: R(F) atrazine=isoproturon>diuron=fipronil>phenmedipham. This order was roughly correlated to log P but much more complex correlations were suggested. The rate of water movement, VWR, widely changed from one matrix to another. Therefore, the pesticide movement, M, in soil microstructures under the action of rain may be described by the equation M = WR R(F).