Modulation of macrophage protease activity by acute administration of O,O,S trimethyl phosphorothioate.
Previous studies showed that acute administration of O,O,S trimethyl phosphorothioate (OOS-TMP), a contaminant in malathion, acephate and fenitrothion, led to increases in metabolic activities, such as, secretion of interleukin 1 and nonspecific esterase, of splenic and peritoneal macrophages. In this report, the effect of OOS-TMP administration on the levels of the neutral proteases, elastase, collagenase and plasminogen activator, in cultures supernatants of peritoneal and splenic macrophages is presented. Acute administration of OOS-TMP elevated collagenase levels only at day 3 following treatment with 10 or 20 mg/kg OOS-TMP. Levels of elastase in culture supernatant of peritoneal and splenic macrophages, on the other hand, was elevated at days 1, 3, 5 and 7 following administration of OOS-TMP. The effect on elastase secretion was dose-dependent at days 5 and 7 after treatment. Levels of plasminogen activator activity in the culture supernatants of splenic macrophages was elevated at day 5 following treatment with both doses of OOS-TMP. At days 1 and 3, the level of plasminogen activator inhibitor was suppressed. However, at days 5 and 7 plasminogen activator inhibitory activity was close to control values. These data show that OOS-TMP administration led to an elevation in the levels of neutral proteases in culture supernatants of peritoneal and splenic macrophages. This elevation indicates that acute OOS-TMP administration alters another parameter of macrophage function, which is elevated following exposure to acute inflammatory stimuli.
Rodgers
K E
KE
Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles 90033.
Ellefson
D D
DD
D000818:Animals; D005260:Female; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D003012:Microbial Collagenase / Q000378:metabolism; D063086:Organothiophosphates / Q000494:pharmacology*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D010960:Plasminogen Activators / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism; D013154:Spleen / Q000166:cytology
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D015849:Plasminogen Inactivators; C019123:O,O,S-trimethyl phosphorothioate; D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D010196:Pancreatic Elastase; D003012:Microbial Collagenase