Macrophage Depletion Protects against Cigarette Smoke-Induced Inflammatory Response in the Mouse Colon and Lung

Abstract

Cigarette smoke (CS) is considered as a major risk factor for pulmonary and intestinal inflammation. CS leads to macrophage infiltration in the mucosae of the lung and colon, inducing the uncontrolled secretion of inflammatory mediators, and thus promoting inflammatory response. In this study, we investigated whether macrophage depletion modulates cigarette smoke (CS)-induced inflammatory response in both the lung and colon. The mice were exposed to CS for 30 min, after which they were rested in a fresh air environment for 30 min. The total duration of exposure to CS was 2 h per day for 4 weeks. Macrophage depletion state was made with the injection of clodronate containing liposome. Individual body weights were measured twice a week, and the mice were sacrificed on day 28. Hematoxylin and eosin (H&E) staining was performed in the lung and colon tissue to determine histological changes. Inflammatory mediators' synthesis was analyzed using ELISA and western blotting. Clodronate liposome treatment ameliorated pathological changes associated with the infiltration of immune cells in the lung and colon. Also, clodronate liposome injected mice showed significantly lower level of inflammatory mediators, including cytokines and chemokine and proteases. Our results indicated that macrophage depletion by clodronate liposome treatment attenuates CS-induced inflammatory response in both the lung and colon.

Intratracheal Ovalbumin Administration Induces Colitis Through the IFN-γ Pathway in Mice

“…However, intratracheal administration of OVA did not alter IL-17A levels in the colons of WT, T-bet deficient, or IFN-γ deficient mice. The IFN-γ pathway is not the only mechanism linking inflammatory bowel disease and pulmonary inflammation; a recent study demonstrated the role of macrophages in cigarette smoke-induced colitis (35). Indeed, we also observed an increase in the number of macrophages in the colonic laminar propria after OVA sensitization (Supplementary Figure 1), thus detailed mechanisms need to be identified in subsequent studies.…”

Epithelial Ablation of Miro1/Rhot1 GTPase Leads to Mitochondrial Dysfunction and Lung Inflammation by Cigarette Smoke

“…All cells were stained using cell type-specific mAb. For four months (chronic) exposure, differential cell counts to check the cell influx in neutrophils and macrophages were performed on cytospin slides with Diff-Quick staining (Cui, Liu, Ip, Liang, & Mak, 2020;Lim, Kim, Lee, Bae, & Kim, 2018). The Diff-Quick staining involves sequential dipping of the slides into different solutions -fixative agent (methanol, blue), solution 1 (eosinophilic, orange), and solution 2 (basophilic, blue) followed by rinsing and drying.…”

Recent trends of NFκB decoy oligodeoxynucleotide-based nanotherapeutics in lung diseases

“…Lipopolysaccharide (LPS), a potent endotoxin in gram-negative bacteria, may activate immune cells (such as dendritic cells and alveolar macrophages) during the course of respiratory tract infections via a special type of receptor known as toll-like receptors (TLRs) [11]. Inflammation can also be induced by hypoxia, for example acute hypoxia in rats with endotoxemia results in alveolar macrophages releasing TNF-, IL-1, IL-6, and TLR-4 [12].…”

“…The critical role of macrophages in controlling lung inflammation is exemplified by macrophage depletion in mice exposed to cigarette smoke. This results in reduced J o u r n a l P r e -p r o o f Journal Pre-proof inflammatory cell infiltration, ameliorated body weight loss and decreased inflammatory cytokines (IL-1β, IL-6, TNF-α) and the chemokine, monocyte chemoattractant protein-1 in bronchoalveolar lavage fluid (BALF) and reduced matrix metalloproteinase-3 protein expression in lung tissue [11].…”