The Responses of Human Neutrophils to Tobacco Smoke Components

Abstract

Tobacco smoking is considered a major modifiable risk factor for periodontal disease. Tobacco contains about 6700 compounds and almost 4000 compounds of these have been identified in tobacco smoke. Nicotine is the addictive ingredient in tobacco and has been shown to affect multiple cellular processes. Cigarette smoke condensate (CSC) is the particulate matter of smoke. It is believed to be a powerful inducer of inflammatory responses. Neutrophils are the first line of host defense and are critical cells in the maintenance of periodontal health through their role in the control of bacteria, but they can also contribute to the progression of periodontal disease by the production and release of reactive oxygen species (ROS). Virulence factors from periodontal pathogens, such as Porphyromonas gingivalis (P. gingivalis), stimulate the respiratory burst of neutrophils. In this dissertation, three studies aimed at understanding the oxidative activity of neutrophils when stimulated with either nicotine, cigarette smoke condensate (CSC) or four other components of tobacco smoke (2-naphthylamine, hydroquinone, acrolein, and acetaldehyde) with or without P. gingivalis supernatant. The release of matrix metalloproteinase-9 (MMP-9) was also examined. ROS production increased significantly when the neutrophils were stimulated with nicotine. P. gingivalis induced the maximum ROS production when compared to all the other components examined. The combination of nicotine and P. gingivalis did not have an additive effect on ROS production. Nicotine significantly increased the MMP-9 release from the neutrophils. On the contrary, CSC inhibited ROS production at all the concentrations examined. The combination of CSC and P. gingivalis resulted in the inhibition of ROS production. MMP-9 release was also increased from the CSC-treated neutrophils. The four other tobacco smoke components examined affected ROS production and MMP-9 release differently. These projects demonstrated that CSC inhibited the ROS production from neutrophils, which can be attributed to several components in tobacco smoke that may include acrolein and hydroquinone. More research is needed to determine the mechanisms of inhibition and if other tobacco components are involved in ROS inhibition