) Cigarette smoking is the major risk factor for the development of emphysema but only a relatively small proportion of cigarette smokers develop this complication. The investigators' work suggests that latent adenoviral infection of the lung adds risk by amplifying cigarette smoke induced inflammation to a level capable of causing emphysematous lung destruction. The investigators propose to test this hypothesis on surgically resected human lung specimens and on cultured cells derived from this tissue. The investigators' first goal is to compare normal regions of the lung, to regions with mild and severe emphysema using laser capture microdissection and micro assay technologies to determine if increased adenoviral DNA results in increased inflammatory gene expression in emphysema. The second group of experiments will determine if cytokines generated from alveolar macrophages obtained from these lungs stimulate adenoviral E1A transfected lung epithelial cells to generate excess inflammatory mediators in vitro. A third group of studies will examine the nature of the migration of neutrophils through the alveolar wall in cigarette smoke induced inflammation to determine the nature and effect of the contact between the polymorphonuclear cell and the alveolar wall elastin network. The fourth set of studies will focus on the nature of adenoviral DNA integration into the host respiratory epithelial cell genome to determine if the site of integration effects the production of inflammatory mediators. Finally, the investigators will determine the genetic susceptibility to latent adenoviral integration in the human lung. The information gathered from these studies will provide new insights into the pathogenesis of emphysema and help explain why some smokers develop emphysema and others do not.
