title: Editor's Highlight: Role of Spleen-Derived Macrophages in Ozone-Induced Lung Inflammation and Injury.
abstract: Macrophages and inflammatory mediators have been implicated in ozone toxicity. In these studies, we used splenectomized (SPX) mice to assess the contribution of splenic monocytes to pulmonary inflammation and injury induced by ozone. Cells and tissue were collected 24-72 h after exposure of mice to air or ozone (0.8 ppm, 3 h). Following ozone exposure, increased numbers of pro-inflammatory CD11b+Ly6CHiand anti-inflammatory CD11b+Ly6CLomonocytes were observed in spleens of control (CTL) mice. CD11b+Ly6CHiand MMP-9+pro-inflammatory macrophages were also observed in lungs of CTL mice after ozone, along with CD11b+Ly6CLoand mannose receptor (MR)+anti-inflammatory macrophages. This was accompanied by increased lung expression of proteins involved in monocyte/macrophage trafficking including CCL3, CCL4, CCR1, and AT1R. Splenectomy resulted in decreases in pro-inflammatory macrophages in the lung and down regulation of CCR2, CCL2, and CCL4, but increases in CD11b+Ly6CLoanti-inflammatory macrophages. CD11b+Ly6G+Ly6C+granulocytic (G)- and monocytic (M)-myeloid derived suppressor cells (MDSC)s were also detected in the lungs and spleens of CTL mice; these increased after ozone exposure. Splenectomy was associated with a decrease in G-MDSCs in the lung, with no effect on M-MDSCs. Changes in lung macrophage subpopulations and MDSCs in SPX mice were correlated with reduced ozone toxicity, as measured by decreases in bronchoalveolar lavage protein content and reduced 4-hydroxynonenal expression in the lung. These data suggest that the spleen is a source of pro-inflammatory/cytotoxic macrophages that contribute to ozone-induced lung injury, inflammation, and oxidative stress.
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Mary
authors.initials: M
authors.lastname: Francis
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Richard
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Cervelli
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Hyejeong
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Mili
authors.initials: M
authors.lastname: Mandal
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Abramova
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gow
authors.affiliation: Department of Environmental and Occupational Health, Rutgers University School of Public Health, Piscataway, New Jersey.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Laskin
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey; laskin@eohsi.rutgers.edu.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D018925:Chemokines / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D051379:Mice; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000473:pathology* / Q000601:surgery; D013156:Splenectomy
chemical_list: D018925:Chemokines; D010126:Ozone
keywords: inflammation.; macrophages; myeloid derived suppressor cells; ozone; spleen