DECREASED CONTENT OF THE IL1-ALPHA PROCESSING ENZYME CALPAIN IN MURINE BONE-MARROW-DERIVED MACROPHAGES AFTER TREATMENT WITH THE BENZENE METABOLITE HYDROQUINONE

Benzene is an important industrial chemical known to produce hematotox icity in mice and humans. Hydroquinone, a major metabolite of benzene, inhibits conversion of the precursor form of IL1 alpha (pre-IL1 alpha ) to IL1 alpha in murine bone marrow-derived macrophages in vitro, and a similar effect can be demonstrated in vivo after treatment of mice with benzene. The protease which converts pre-IL1 alpha to IL1 alpha i s calpain. We examined decreases in calpain content in bone marrow-der ived macrophages as a possible mechanism underlying hydroquinone-induc ed decreases in pre-IL1 alpha conversion. Hydroquinone, at concentrati ons which were not overtly cytotoxic, decreased total calpain activity in macrophages by 10-30%. Using immunoblot analysis macrophage calpai n II levels were shown to be decreased by approximately 50% after trea tment with hydroquinone. Under the same conditions, no changes were ob served in calpain I content using immunoblot analysis. These data show that decreased calpain II content represents a potential mechanism of hydroquinone-induced inhibition of pre-IL1 alpha processing, and may contribute to benzene-induced alterations in bone marrow stromal cell function and myelotoxicity.