The objectives of this project are to develop procedures for (1) determining the potential of agents in causing lung damage and (2) detecting pulmonary injury and monitoring that injury as it progresses towards or away from the disease state. Methods for the estimation of injury potential involves the use of purified cell populations isolated from the lungs and the reaction of those cells to toxic agents. Methods for the detection of pulmonary injury involve the use of pulmonary lavage effluents and the identification of markers of cellular injury. Two cell populations have been isolated from the lungs of rabbits. Clara cells from the airway epithelium have been isolated and purified to as much as 95% with 97% viability as measured by exclusion of trypan blue. Type II cells have also been isolated and purified to as much as 85% with 88% viability. Incubation of clara cells and Type II cells with naphthalene revealed that Type II cells were considerble more senstitive to the toxicity of the agent than Clara cells. Incubtion of cells with naphthalene (lmM) for a period of one hour resulted in 1 20% loss in viability of the Type II cells whereas Clara cells and alveolar macrophages were unaffected. Lavage effluents from the lungs of rats treated with silica by intratracheal injection showed elevated levels of some biochemical parameters. Increases were all dose- and time-dependent. These investigations indicate that isolated cells could be used to test the cellular toxicity of chemical agents and that lavage effluents from the lungs of animals exposed to toxic agents may be used for the detection of pulomonary lung injury.
