Comparison of Aryl Hydrocarbon Hydroxylase Induction in Cultured Blood Lymphocytes and Pulmonary Macrophages

Abstract

A B S T R A C T Aryl hydrocarbon hydroxylase induction was studied in cultured peripheral blood lymphocytes and pulmonary alveolar macrophages from 15 smokers and 8 nonsmokers with a variety of pulmonary diseases. Enzyme levels in lymphocytes from cigarette smokers cultured in medium without an inducing agent were 57±6 mU/106 cells (mean+SEM), while enzyme levels in lymphocytes from nonsmokers were 20+2 mU/106 cells (P < 0.001). When lymphocytes were cultured in the presence of the inducing agent, benzo-(a)anthracene, enzyme activity was increased to 168 +23 mU/106 cells in smokers' cells and 99+22 mU/106 cells in lymphocytes from nonsmokers (P < 0.04).When noninduced enzyme values in cultured macrophages were compared, smokers' cells had enzyme levels of 45+5 mU/106 cells, whereas nonsmokers had enzyme activity of 24±2 mU/106 cells (P < 0.002). However, pulmonary macrophages from smokers or nonsmokers, cultured in the presence of benzo(a)-anthracene, had similar levels of induced enzyme activity (P > 0.1). A positive correlation was observed for nonsmokers (r = 0.596, P > 0.1 <0.2) or smokers (r = 0.640, P < 0.04), when enzyme values for noninduced cultures of macrophages and lymphocytes from individual patients were simultaneously compared. Enzyme values for macrophages and lymphocytes cultured in the presence of an inducer also revealed a positive correlation for individual smokers (r = 0.801, P < 0.001) or nonsmokers (r = 0.785, P < 0.01). Inducibility (expressed as fold-induction) for macrophages Dr positively correlated (r = 0.889, P < 0.001 for nonsmokers and r = 0.942, P < 0.001 for smokers). These results indicate that the capacity for aryl hydrocarbon hydroxylase induction is similar whether tested in lymphocytes or pulmonary macrophages from this group of pulmoniary disease patients.

The Role of a Mitochondrial Pathway in the Induction of Apoptosis by Chemicals Extracted from Diesel Exhaust Particles

“…Among the cell types that participate in ROS production in response to PM deposition in the lung is the macrophage (15)(16)(17)(18)(19). We are particularly interested in the role of macrophages in PM-induced inflammation for the following reasons: 1) macrophages are the principal cells that remove DEP and other PM from the bronchoalveolar region of the lung (20,21); 2) macrophages phagocytose DEP, leading to the accumulation of toxic intracellular DEP concentrations (19); and 3) macrophages are endowed with enzymatic pathways for ROS generation, including inducible cytochrome P450-dependent pathways (22)(23)(24).…”

Induction of Ouabain-resistant Mutation and Sister Chromatid Exchanges in Chinese Hamster Cells with Chemical Carcinogens Mediated by Human Pulmonary Macrophages

“…The variation caused by experimental miiethodology wasiminimal. In addition, PAM had been cultivated for 7-8 d before use to minimize metabolic changes cauised by exogenous factors, e.g., tobacco smoking and drug treatments, in the donors; chemical constitutents from cigarette tar were found to induice AHH activity in PAM (5,23,24).…”

Human Skin Aryl Hydrocarbon Hydroxylase

“…AHH activity was proportional to skin protein up to a concentration of5-7.5 mg ofprotein in both polycyclic aromatic hydrocarbon carcinogens. The enzyme has been found in numerous human tissues including liver (25,26), lung (27), placenta (28), pulmonary alveolar macrophages (29), lymphocytes (30), and skin (20,21). Recent (36).…”