Effect of complement fixation on the release of lysosomal enzymes from rabbit alveolar macrophages.
Macrophage lysosomal enzymes that have specificities for substrates found in mammalian tissue may contribute to the tissue damage observed in chronic inflammatory diseases. Although a variety of agents that stimulate the release of hydrolases from peritoneal macrophages have been identified, little work has been done to establish the conditions and specific stimuli responsible for enzyme release by alveolar macrophages (AM). To assess the effect of phagocytosis by AM on the release phenomenon, hydrolytic enzymes normally sequestered in AM lysosomes were quantified in the supernatant fluids of phagocytosing and non-phagocytosing AM monolayers in both the presence and absence of serum. Maximum release occurred under conditions known to favor complement fixation by the classical or alternative pathways. Thermal destruction or immune fixation of serum complement before use in culture reduced the magnitude of release to that observed in cultures incubated in the complete absence of serum. Phagocytosis was not essential for release, since cells exposed to particles but treated with a known inhibitor of phagocytosis (cytochalasin B) still showed maximal release in the presence of fresh serum. These data are interpreted to indicate that a heat-labile component of serum, probably a by-product of complement fixation, was primarily responsible for the hydrolase release by AM. On the basis of these findings, individuals suffering from chronic pulmonary disease may suffer acute episodes of lung destruction from endogenous AM enzymes upon the inhalation of materials capable of fixing complement.
D000818:Animals; D003165:Complement System Proteins / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D006596:Hexosaminidases / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology* / Q000502:physiology; D010587:Phagocytosis; D011650:Pulmonary Alveoli / Q000166:cytology; D011817:Rabbits; D015054:Zymosan
D003165:Complement System Proteins; D015054:Zymosan; D006596:Hexosaminidases; D005966:Glucuronidase