ARB Research Seminar
This page updated June 19, 2013
Genetic Susceptibility and Immune System Responses to Particulate Air Pollution
David Diaz-Sanchez, Ph.D., David Geffen School of Medicine, University of California, Los Angeles
April 09, 2007
Cal EPA Headquarters, 1001 "I" Street, Sacramento, CA
Airborne particulates and gases related to anthropomorphic activities, e.g. ambient "air pollution," are important environmental agents that can modulate the immune system and enhance and even initiate respiratory and cardiovascular disease. These pollutants can impact directly and indirectly on multiple branches of the immune system.
Current results indicate that diesel exhaust particles (DEP) or secondhand smoke (SHS) can enhance allergic responses by increasing allergic antibody production, boosting histamine release or by targeting specialized cells in the immune pathway to promote a milieu that favors allergy. Pollutants may act via activation of oxidative stress. Airway antioxidant defenses to combat these effects are mediated, in part, by enzymatic antioxidants primarily Phase II enzymes. Using human airway exposure models, we show that individuals with common functional variant alleles that result in either the total absence or a marked alteration in the enzyme activity of members of this family are at greatly increased risk to the pro-inflammatory and pro-allergic effects of both DEP and SHS.
Research shows that oxidant pollutants preferentially target the immune system of children due to a reduced ability in children to produce Phase II enzymes that regulate the severity of the inflammatory response to these oxidants. In addition, in a murine model we show how in utero exposure can affect future asthma outcomes and how these pollutants may also have transgenerational effects that can be manifested in the grandchildren of exposed pregnant mice. Finally, we discuss our human clinical studies that show that enhancement of Phase II enzymes constitute an important novel therapeutic strategy to combat the adverse effects of air contaminants on the immune system.
David Diaz-Sanchez, Ph.D., is an Associate Professor of Medicine at the David Geffen School of Medicine at the University of California, Los Angeles.
Dr. Diaz-Sanchez main area of focus has been on how air pollution can both induce and exacerbate allergies and asthma. Dr. Diaz-Sanchez work has used diesel exhaust particles and environmental tobacco smoke as model particulate pollutants. Dr. Diaz-Sanchez has focused primarily on human in vivo models and has established both nasal and inhalation models that have served to show how these particles can impact different cell types to promote inflammatory and pro-allergic responses.
Along with Dr. Gong at Rancho Los Amigos (Henry Gong Jr., M.D. currently serves as Board Member with the Air Resources Board), Dr. Diaz-Sanchez runs one of the four diesel inhalation chambers currently in use in the United States. In collaboration with colleagues at the University of Southern California, he has published on how antioxidant enzyme genes can confer susceptibility or protection to oxidant pollutants. Dr. Diaz-Sanchez is currently investigating novel methods to combat the effects of particulate pollutants and is working with UCLA colleagues using a therapeutic approach and with Mexican colleagues using a dietary approach.
Dr. Diaz-Sanchez joined UCLA in 1992 from the United Kingdom after finishing his Ph.D. in immunology at Guys Hospital, London studying the role of ricin on IgE regulation. Since that time his work has focused primarily on the role of the environment in modulating immune function. Dr. Diaz-Sanchez is a member of the UCLA asthma Center, the USC/UCLA Children's Environmental Health Center and a member of the Environmental Health Center of Southern California. Since 1998 he has served as both consultant and member of the Clean Air Scientific Advisory Committee for the U.S. Environmental Protection Agency.