Regulation of ozone-induced lung inflammation and injury by the β-galactoside-binding lectin galectin-3

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Abstract

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 24–72 h after exposure (3 h) of WT and Gal-3−/− mice to air or 0.8 ppm 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 (Ly6GLy6Chi) and anti-inflammatory (Ly6GLy6Clo) macrophages. Increases in both macrophage subpopulations were observed following ozone inhalation. Loss of Gal-3 resulted in a decrease in Ly6Chi macrophages, with no effect on Ly6Clo 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.

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