Mechanism of the modulation of murine peritoneal cell function and mast cell degranulation by low doses of malathion
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Published on: November 1, 2013
1Livingston Research Center, University of Southern California, School of Medicine, Los Angeles 90033.
Abstract:
Malathion is a widely used organophosphate pesticide that modulates immune function at noncholinergic doses. Previous studies showed that this alteration in immune function was the result of enhanced macrophage function. In the present study, the effects of low doses of purified malathion (as low as 0.25 mg/kg malathion) administered orally to mice enhanced the respiratory burst of peritoneal cells. Microscopic examination of the peritoneal cells showed that mast cells were degranulated within 4 hr after malathion administration. The amount of beta-hexosaminidase, an enzyme released upon immunologic degranulation of mast cells, in the peritoneal lavage fluid of malathion-treated mice was also significantly elevated with 4 hours after malathion administration. Treatment of RBL-1, a rat basophilic cell line, cells with malathion, parathion or paroxon in vitro also led to the release of beta-hexosaminidase with paraoxon being the most potent. Further examination of the peritoneal cells of malathion-treated mice showed that the percentage of phagocytic peritoneal cells ingesting mast cell granules and the number of granules ingested per cell were elevated. These data suggest that malathion may enhance the respiratory burst of peritoneal cells through degranulation of peritoneal mast cells and the subsequent exposure to peritoneal cells to mast cell mediators.
Insights
Low doses of the pesticide malathion boost immune cell activity in mice by triggering mast cell degranulation. This process enhances macrophage function and the respiratory burst, indicating a novel immune-modulating pathway for organophosphate pesticides.
Area of Science:
- Immunology
- Toxicology
- Cell Biology
Background:
- Organophosphate pesticides, like malathion, are known to modulate immune function.
- Previous research suggests this modulation involves enhanced macrophage activity.
- The specific mechanisms underlying malathion's noncholinergic immune effects require further elucidation.
Purpose of the Study:
- To investigate the effects of low-dose malathion on immune cell function in mice.
- To determine if malathion induces mast cell degranulation and its impact on peritoneal cells.
- To explore the role of mast cell mediators in malathion-induced immune enhancement.
Main Methods:
- Oral administration of purified malathion to mice at doses as low as 0.25 mg/kg.
- Microscopic examination of peritoneal cells to assess mast cell degranulation.
- Quantification of beta-hexosaminidase in peritoneal lavage fluid.
- In vitro treatment of RBL-1 cells with malathion, parathion, and paraoxon.
- Analysis of phagocytic activity of peritoneal cells towards mast cell granules.
Main Results:
- Low-dose malathion significantly enhanced the respiratory burst of peritoneal cells in mice.
- Mast cells in the peritoneal cavity showed degranulation within 4 hours of malathion administration.
- Elevated levels of beta-hexosaminidase were detected in peritoneal lavage fluid post-malathion treatment.
- In vitro studies confirmed that malathion, parathion, and paraoxon induce beta-hexosaminidase release from mast cells.
- Malathion treatment increased the phagocytosis of mast cell granules by peritoneal cells.
Conclusions:
- Malathion exposure at low doses can enhance peritoneal cell respiratory burst.
- Mast cell degranulation appears to be a key mechanism mediating malathion's immune-enhancing effects.
- The release of mast cell mediators following malathion exposure may contribute to increased macrophage function.
