Diabetes is associated with increased sensitivity of alveolar macrophages to urban particulate matter exposure

Many epidemiological studies and animal experiments have shown that individuals with preexisting diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM) are more susceptible to particulate matter (PM)-related health problems. However, the mechanisms underlying this susceptibility are still unclear. PM has been shown to affect macrophage functions. We hypothesized that exposure to PM in the setting of DM and high glucose levels would result in enhanced macrophage activation. Rabbits were rendered diabetic with alloxan administered intravenously. Blood glucose concentration was measured daily for the first several weeks and weekly thereafter using a blood glucose meter. After 9 months of diabetes (blood glucose great than 450 mg/dl), rabbits were sacrificed and bronchoalveolar lavage was performed to collect alveolar macrophages. Alveolar macrophages were exposed in vitro to urban particulate matter SRM 1648 (U-PM). Our results showed that U-PM caused dose-dependent cytotoxic effects, and these effects were significantly higher in macrophages obtained from DM rabbits than those from normal rabbits. Reactive oxygen species (ROS) generation in macrophages from DM rabbits with exposure to U-PM was also greater than in macrophages from normal rabbits. Our results also showed that exposure of macrophages to U-PM caused an increase in cytokine mRNA expression level and activity of matrix metalloproteinase 9 (MMP-9), but not MMP-2, and that these effects were greater in macrophages from DM rabbits. These results demonstrate that U-PM caused severe oxidative stress in macrophages from DM rabbits and up-regulation of cytokine expression and MMP-9 activity. (C) 2009 Elsevier Ireland Ltd. All rights reserved.