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Modulation of macrophage protease activity by acute administration of O,O,S trimethyl phosphorothioate
1Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles 90033.
Abstract:
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.
Insights
Acute exposure to O,O,S trimethyl phosphorothioate (OOS-TMP), a pesticide contaminant, increases neutral protease levels in macrophages. This indicates OOS-TMP alters macrophage function, similar to inflammatory stimuli.
Area of Science:
- Immunology
- Toxicology
- Biochemistry
Background:
- O,O,S trimethyl phosphorothioate (OOS-TMP) is a contaminant found in pesticides like malathion.
- Previous research indicated OOS-TMP increases metabolic activity in splenic and peritoneal macrophages.
- Macrophage activation is crucial in immune responses and inflammation.
Purpose of the Study:
- To investigate the effect of OOS-TMP administration on neutral protease levels in macrophages.
- To determine the specific neutral proteases affected by OOS-TMP exposure.
- To assess the dose and time-dependent effects of OOS-TMP on macrophage function.
Main Methods:
- Primary cultures of peritoneal and splenic macrophages were established.
- Macrophages were treated with varying doses of OOS-TMP (10 or 20 mg/kg).
- Levels of collagenase, elastase, and plasminogen activator in culture supernatants were measured at different time points (days 1, 3, 5, 7).
Main Results:
- OOS-TMP administration elevated collagenase levels at day 3 post-treatment.
- Elastase levels were significantly increased at days 1, 3, 5, and 7, showing a dose-dependent effect at later time points.
- Plasminogen activator activity increased at day 5, while plasminogen activator inhibitor levels were suppressed early on but returned to baseline later.
Conclusions:
- Acute OOS-TMP exposure elevates neutral protease levels, including collagenase, elastase, and plasminogen activator, in macrophages.
- These findings demonstrate that OOS-TMP alters macrophage function, specifically protease secretion.
- The observed changes in protease activity suggest OOS-TMP acts as an inflammatory stimulus, impacting macrophage immune responses.