University of Alabama at Birmingham
How Does Cadmium in Cigarette Smoke Increase Risk of Hospital-Acquired Pneumonia?
One complication of cigarette smoking is the increased susceptibility of hospital-acquired pneumonia (HAP)—pneumonia that occurs 48 hours or more after hospital admission. HAP is one of the most common infections that occur during hospitalization. Alveolar macrophages are an important type of cell in the lung that plays an integral role in the body's defense against respiratory infections. Cigarette smoke contains more than 4,500 compounds, some of which are carcinogens, toxins, and metals. Cadmium, one of the metals present in cigarette smoke , inhibits alveolar macrophage function, preventing their ability to fight lung infections. We will determine the mechanism(s) by which cigarette smoke increases the susceptibility of smokers to HAP, thereby permitting the potential design of a therapeutic agent.
Update: Reactive oxygen species are chemical substances that are a component of the killing response of immune cells to microbial invasion. We determined that cigarette smoke diminished reactive oxygen species production in lung macrophages, which are critical for immune-system defense. We founded that cadmium from cigarette smoke mediated these changes by inhibiting a protein called GTPase Rac2. Taken together, our observations suggest that therapies to maintain Rac2 activity in lung macrophages restore immune-system defense against respiratory pathogens and diminish the prevalence and severity of hospital acquired pneumonia in people who smoke.