Asbestos has long been known to cause primary lung cancer, mesothelioma, pleuropulmonary fibrosis, and pleural effusions in humans and experimental animals. Many studies have focused on fiber-induced fibroproliferative and inflammatory processes in the lung; however, very few studies have examined alterations in the pleural space, an important target site of fiber-induced disease. Pleural inflammation is a common feature of asbestos-related disease, but little is known about the factors that regulate this process. Therefore the objective of this proposal is to determine the role of pleural mesothelial cell adhesion molecules in mineral fiber-induced inflammation. This research is designed to test the hypothesis that alterations in pleural mesothelial cell adhesion molecule expression correlate with inflammation. The research design involves using in vivo and in vitro techniques to determine pleural mesothelial cell adhesion molecule expression following asbestos exposure.
Specific aims are to (1) determine if there are alterations in intercellular adhesion molecule-1 (ICAM1) and vascular adhesion molecule-1 (VCAM-1) expression following mineral fiber exposure; (2) determine if these alterations are particle-type specific; and to (3) determine if these alterations are dependent upon direct interaction of mineral fibers with target cells or mediated by indirect factors. The results of this work will provide the first description of adhesion molecule expression in pleural mesothelial cells from the rat, the animal model most commonly used in fiber toxicology. These data will provide new information concerning mechanisms of inflammation in the pleural space.
