Benzo (a)pyrene exposure reduces CD54 expression on alveolar macrophages and alters apoptosis and inflammatory responses in the lungs

Abstract

The study investigates the role of intracellular cell adhesion molecule-1 (ICAM-1, CD54) expression in alveolar macrophages and associated molecular alterations in benzo (a)pyrene (BaP)-induced lung tumor-bearing mice that provide more profound insight into immune mechanisms in lung cancer. Lung tumors were induced by administering BaP (50 mg/kg body weight, twice a week for four weeks) orally. A single-alveolar cell suspension was stained with fluorescently conjugated antibodies for the demarcation of alveolar macrophages (F4/80 and CD11b cells). CD54 expression on different alveolar macrophages was analyzed based on CD11b/F4/80 gating. The mortality and cell cycle were studied by 7-AAD and PI staining, respectively, and flow cytometric analysis. Our results suggest that CD54 expression is significantly decreased on CD11b+ alveolar macrophages and CD11b+/F4/80+ interstitial macrophages. BaP treatment increased cell mortality, and cell cycle progression was inhibited. The expression of proapoptotic (BAX and Caspase 3) and antiapoptotic (Bcl-2 and Cytochrome C) genes was reduced, but the expression of proinflammatory (IL-6, IL-10, and TNF-α) and anti-inflammatory (IFN-γ) genes was significantly increased, but that of TGF-β was decreased. Overall, BaP-induced tumors suppress CD54 expression on alveolar macrophages, induce cellular mortality, inhibit the cell cycle, and alter the expression of pro-apoptotic, anti-apoptotic, and anti-inflammatory genes in murine lungs.