Regulation of ozone-induced lung inflammation and injury by the β-galactoside-binding lectin galectin-3.
Macrophages play a dual role in ozone toxicity, contributing to both pro- and anti-inflammatory processes. Galectin-3 (Gal-3) is a lectin known to regulate macrophage activity. Herein, we analyzed the role of Gal-3 in the response of lung macrophages to ozone. Bronchoalveolar lavage (BAL) and lung tissue were collected 24-72h after exposure (3h) of WT and Gal-3(-/-) mice to air or 0.8ppm ozone. In WT mice, ozone inhalation resulted in increased numbers of proinflammatory (Gal-3(+), iNOS(+)) and anti-inflammatory (MR-1(+)) macrophages in the lungs. While accumulation of iNOS(+) macrophages was attenuated in Gal-3(-/-) mice, increased numbers of enlarged MR-1(+) macrophages were noted. This correlated with increased numbers of macrophages in BAL. Flow cytometric analysis showed that these cells were CD11b(+) and consisted mainly (>97%) of mature (F4/80(+)CD11c(+)) proinflammatory (Ly6GLy6C(hi)) and anti-inflammatory (Ly6GLy6C(lo)) macrophages. Increases in both macrophage subpopulations were observed following ozone inhalation. Loss of Gal-3 resulted in a decrease in Ly6C(hi) macrophages, with no effect on Ly6C(lo) macrophages. CD11b(+)Ly6G(+)Ly6C(+) granulocytic (G) and monocytic (M) myeloid derived suppressor cells (MDSC) were also identified in the lung after ozone. In Gal-3(-/-) mice, the response of G-MDSC to ozone was attenuated, while the response of M-MDSC was heightened. Changes in inflammatory cell populations in the lung of ozone treated Gal-3(-/-) mice were correlated with reduced tissue injury as measured by cytochrome b5 expression. These data demonstrate that Gal-3 plays a role in promoting proinflammatory macrophage accumulation and toxicity in the lung following ozone exposure.
Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States. Electronic address: sunilva@pharmacy.rutgers.edu.
Vasanthi R
VR
Sunil
Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States. Electronic address: maryfranrutgers@gmail.com.
Mary
M
Francis
Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States. Electronic address: kinalv5@gmail.com.
Kinal N
KN
Vayas
Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States. Electronic address: j.cervelli@pharmacy.rutgers.edu.
Jessica A
JA
Cervelli
Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States. Electronic address: choi@eohsi.rutgers.edu.
Hyejeong
H
Choi
Department of Environmental and Occupational Medicine, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, United States. Electronic address: jlaskin@eohsi.rutgers.edu.
Jeffrey D
JD
Laskin
Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States. Electronic address: laskin@eohsi.rutgers.edu.
Debra L
DL
Laskin
D000818:Animals; D005260:Female; D005697:Galactosides / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury / Q000139:chemically induced* / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism*
D005697:Galactosides; D037502:Galectin 3; D037161:Galectins; C007816:beta-galactoside; D010126:Ozone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
Flow cytometry; Gal-3; MDSC; Macrophage phenotype; Ozone