Mobilization of leucocytes and subsequent release of histamine and lysosomal enzymes into the peritoneal and pleural cavities of rats by actinomycin D (dactinomycin).

Abstract

1. The effects of intraperitoneal injections of actinomycin D on the temporal characteristics of the accumulation of the inflammatory exudate and cells into the peritoneal and pleural cavities were studied in male Sprague Dawley rats. 2. A measurable quantity of the exudate appeared in both cavities within 24 h and reached maxima in the peritoneal and pleural cavities on the fourth and third days, respectively. Thereafter, the accumulated volume of liquid decreased progressively in the peritoneal cavity but stayed more or less at about the same level in the pleural cavity until the sixth day. 3. The pooled peritoneal and pleural exudates contained neutrophils, macrophages, mast cell and eosinophils. The leucocyte infiltration occurred in two phases, the maximum cell numbers being found on the third and fifth days. A precipitous fall in the number of leucocytes occurred on the fourth day. Neutrophils and macrophages accounted for 85-95% of the total number of leucocytes. 4. The supernatant of the inflammatory exudate after centrifugation at 3,000 g contained histamine and the soluble lysosomal enzyme proteins, acid phosphatase and beta-glucuronidase until the sixth day following the initial dose of actinomycin D. 5. It is suggested that the release of lysosomal enzymes in the exudate, subsequent to leucocyte mobilization and the release of histamine from the mast cells, are probably involved in the genesis of inflammatory conditions induced by actinomycin D.