5d2b5cef9acb65f8eca28f823fe21e29 toxics-12-00530.pdf 62f15ad947db435169a3f3a528f7cb0b4f6672ef toxics-12-00530.pdf 05f33ec9ca3be6d364c80e645dcc70660026f5e3375d43da6a0679f96f6014ef toxics-12-00530.pdf Title: Immunological Effects of Diesel Particles in a Murine Model of Healthy Mice Subject: Introduction: Exposure to environmental pollutants such as diesel exhaust particles (DEP) increases the risk of respiratory disease exacerbation. However, the possible effects of these particles on the general population remain poorly understood. The present study aimed to assess the immunomodulatory and inflammatory effects of the inhalation of DEP in a model of healthy mice undergoing short-, mid- and long-term exposure. Materials and Methods: BALB/c ByJ mice were randomly divided into five experimental groups. The control group received three intranasal instillations of saline over 8 days while the other four groups received intranasal instillations of 150 g of DEP 3 days per week for 8, 17, 26, and 53 days. Lung function assessment and flow cytometry were performed. Results: In lung tissue, intranasal exposure to DEP decreased total monocytes (p < 0.015 in all groups). At 26 days, a reduction in inflammatory monocytes and an increase in resident monocytes were observed, p = 0.001 and 0.0001, respectively. Eosinophils and neutrophils decreased at 26 days (p = 0.017 and p = 0.041, respectively). The intranasal challenges of DEP increased the total population of dendritic cells (DC) at 26 and 53 days (p = 0.017 and p = 0.022, respectively) and decreased the total and alveolar populations of macrophages (p < 0.003 for all groups compared to control), while interstitial macrophage populations increased over the time period (p = 0.0001 for all groups compared to control). Conclusions: Continuous DEP exposure triggers immune mechanisms that predispose healthy individuals to a pro-inflammatory and hyper-reactive microenvironment. This mouse model provides evidence of the capacity of DEP to increase DC, interstitial macrophages, and resident monocytes. Keywords: pollution; lung inflammation; macrophages; exposure; monocyte Author: David Soler-Segovia, Miquel de Homdedeu, Silvia Sánchez-Díez, Christian Romero-Mesones, David Espejo, Fopke Marain, Jeroen Vanoirbeek, Xavier Munoz and María-Jesús Cruz Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Jul 23 16:30:58 2024 CEST ModDate: Tue Jul 23 16:33:09 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2197720 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JGBJTI+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 VVSYYB+EURM10 Type 1 Builtin yes yes yes 16 0 OAAYZY+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 JQFJUN+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 FZJJRB+URWPalladioL-Ital 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MacRoman yes yes no 681 0 PPIING+Arial,Bold CID TrueType Identity-H yes yes yes 684 0 PPIJFE+Arial CID TrueType Identity-H yes yes yes 690 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-04-23 02:43:46 CEST RepresentationInformation: toxics-12-00530.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-04-22 15:21:43 CEST Size: 2197720 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 939 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Animals Destination: subsection.2.1 Item: Title: Diesel Exhaust Particles (DEP) Destination: subsection.2.2 Item: Title: Experimental Design Destination: subsection.2.3 Item: Title: Lung Function Assessment Destination: subsection.2.4 Item: Title: Bronchoalveolar Lavage Destination: subsection.2.5 Item: Title: DEP-Uptake Analysis Destination: subsection.2.6 Item: Title: Flow Cytometry Destination: subsection.2.7 Item: Title: Data Analysis Destination: subsection.2.8 Item: Title: Results Destination: section.3 Children: Item: Title: Lung Function Assessment Destination: subsection.3.1 Item: Title: Bronchoalveolar Lavage Destination: subsection.3.2 Item: Title: DEP-Uptake Analysis Destination: subsection.3.3 Item: Title: Flow Cytometry Destination: subsection.3.4 Item: Title: Discussions Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Immunological Effects of Diesel Particles in a Murine Model of Healthy Mice Author: David Soler-Segovia, Miquel de Homdedeu, Silvia Sánchez-Díez, Christian Romero-Mesones, David Espejo, Fopke Marain, Jeroen Vanoirbeek, Xavier Munoz and María-Jesús Cruz Subject: Introduction: Exposure to environmental pollutants such as diesel exhaust particles (DEP) increases the risk of respiratory disease exacerbation. However, the possible effects of these particles on the general population remain poorly understood. The present study aimed to assess the immunomodulatory and inflammatory effects of the inhalation of DEP in a model of healthy mice undergoing short-, mid- and long-term exposure. Materials and Methods: BALB/c ByJ mice were randomly divided into five experimental groups. The control group received three intranasal instillations of saline over 8 days while the other four groups received intranasal instillations of 150 g of DEP 3 days per week for 8, 17, 26, and 53 days. Lung function assessment and flow cytometry were performed. Results: In lung tissue, intranasal exposure to DEP decreased total monocytes (p < 0.015 in all groups). At 26 days, a reduction in inflammatory monocytes and an increase in resident monocytes were observed, p = 0.001 and 0.0001, respectively. Eosinophils and neutrophils decreased at 26 days (p = 0.017 and p = 0.041, respectively). The intranasal challenges of DEP increased the total population of dendritic cells (DC) at 26 and 53 days (p = 0.017 and p = 0.022, respectively) and decreased the total and alveolar populations of macrophages (p < 0.003 for all groups compared to control), while interstitial macrophage populations increased over the time period (p = 0.0001 for all groups compared to control). Conclusions: Continuous DEP exposure triggers immune mechanisms that predispose healthy individuals to a pro-inflammatory and hyper-reactive microenvironment. This mouse model provides evidence of the capacity of DEP to increase DC, interstitial macrophages, and resident monocytes. 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