Di-(2-ethylhexyl) phthalate enhances the release of lysosomal enzymes from alveolar macrophages during phagocytosis

Lung tissue damage, histologically similar to protease induced lung lesions, has been previously demonstrated in animals exposed to the plasticizer, di-(2-ethylhexyl)phthalate (DEHO). In an attempt to identify the mechanism responsible for this damage, we have examined the effect of DEHP on alveolar macrophages. Serum solubilized DEHP has a significant effect on both the phogocytosis of latex particles and lysosomal enzyme released from rabbit alveolar macrophages. Pre-exposure to 2 mg% DEHP caused a 2-fold increase in the rate of phagocytosis and an 8-fold and 10-fold increase, respectively, in the release of the lysosomal hydrolases β-glucuronidase and acid phosphatase. Although exposure to 2 mg% DEHP caused an 8-fold increase in in vitro cell death, pre-exposure to DEHP had only minimal effect on death during subsequent cell culture, as indicated by measurement of dye exclusion and the release of the cytosolic enzyme lactate dehydrogenase. The relationship between the DEHP induced increase in lysosomal enzyme release from alveolar macrophages and the pathological and histological effects of DEHP on pulmonary tissue is discussed, particularly with respect to patients receiving multiple blood transfusions.