The Induction of Lysosomal Enzyme Release from Leucocytes of Normal and Emphysematous Subjects and the Effects of Tobacco Smoke upon Phagocytosis

Abstract

1. The lysosomal enzymes of circulating polymorphonuclear leucocytes contain a potent elastase; release of this enzyme within the lung is thought to be responsible for the destruction of elastic tissue in pulmonary emphysema. 2. The release of lysosomal enzymes from blood leucocytes of normal and emphysematous subjects during phagocytosis of particulate material was studied In vitro. Acid phosphatase and acid ribonuclease were used as markers of lysosomal enzyme release, no sufficiently sensitive assay for elastase being available. Cigarette smoke was separated into ‘particulate’ and ‘soluble’ fractions. In a preliminary study, the particulate fraction stimulated enzyme release; in the experiments reported here, latex particles were used to produce this effect. 3. Approximately one-third of the total lysosomal enzyme content was released to the exterior of the cell during phagocytosis of latex particles. In this respect there was no difference between normal and emphysematous subjects. 4. The effects of the non-particulate soluble fraction of cigarette smoke on phagocytosis-induced enzyme release were studied. This fraction inhibited enzyme release from polymorphonuclear leucocytes of normal subjects but not from those of emphysematous patients. When the ‘cigarette-smoke solution’ was replaced by the respiratory inhibitor, antimycin A, a similar inhibition of enzyme release occurred. The inhibition of phagocytosis in cells of normal subjects is presumed to be due to a respiratory inhibitor such as carbon monoxide in the soluble fraction of the smoke. We postulate that the polymorphonuclear leucocytes of emphysematous patients are adapted to hypoxic conditions so that inhibition of enzyme release does not occur.