EFFECTS OF MALATHION METABOLITES ON DEGRANULATION OF AND MEDIATOR RELEASE BY HUMAN AND RAT BASOPHILIC CELLS

Abstract

In the present study, the effects of malathion and malathion derivatives on histamine and β-hexosaminidase release by RBL-1 cells, rat peritoneal mast cells (RPMC), and human peripheral blood basophils (HPBB) and cutaneous mast calls were examined. One hour of incubation of RBL-1 cells with all organophosphate compounds tested, except for malathion and malathion monoacid, led to an increase in histamine release. β-Hexosamini dase, an enzyme released by basophilic cells and a biochemical marker of degranulation, was not released from RBL-1 cells after 1 h of exposure to organophosphate compounds. Within 4 h, all compounds tested increased the release of histamine and β-hexosamini dase. Longer exposures led to a decrease in the concentration of the compound that was required to cause mediator release. Exposure of RPMC to organophosphate compounds, with the exception of malathion monoacid and malathion (30 min) or malathion mono acid (1 h), led to the release of histamine, but not β-hexosaminidase. Incubation of HPBB with malaoxon (51.4 ± 2.8% total histamine released), malathion diacid (25.7 ± 2.9%), β-malathion monoacid (31.4 ± 2.8%), and isomalathion (57.1 ± 17.1%) for 1 h led to the release of histamine. Only malaoxon and isomalathion caused ^-hexosaminidase release from HPBB after a 1-h incubation. Incubation of cutaneous mast cells with mala oxon and fi-monoacid for 4 h led to increased release of histamine and β-hexosaminidase at levels comparable to compound 48/80. These data suggest that malathion metabolites can cause rapid release of histamine from basophilic cells from a variety of origins and species. With prolonged incubation, malathion itself caused the release of mast-cell media tors, suggesting that the cells may be capable of metabolizing malathion. These data also indicate a disparity between the release kinetics of two different mast-cell mediators con tained in granules by organophosphates, and that there are different mechanisms of medi ator release.

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Kathleen Rodgers

Address correspondence to Dr. Kathleen Rodgers, Livingston Research Center, University of Southern California, School of Medicine, 1321 N. Mission Rd., Los Angeles, CA 90033, USA.