METABOLIC-INHIBITORS AS TOOLS TO DELINEATE PARTICIPATION OF DISTINCT INTRACELLULAR PATHWAYS IN ENHANCEMENT OF LACTOSE-INDUCED DISSOCIATION OF NEUTROPHIL AND THYMOCYTE AGGREGATES FORMED BY MEDIATION OF A PLANT LECTIN

Signaling processes in the course of the formation of the lectin-media ted aggregates may partake in conveying enhanced stability to the cell clusters. To prove the validity of this reasoning in a model, we have studied the impact of addition of three metabolic inhibitors (N-ethyl maleimide, nordihydroguaiaretic acid, and trifluoperazine) on lactose- dependent dissociation of cell aggregates, formed in the presence of t he galactoside-binding mistletoe lectin. Using both human neutrophils and rat thymocytes to avoid measurement of responses restricted to a s ingle cell type, an enhanced dissociation of lectin-formed cell aggreg ates was observed, when lactose and an inhibitor were present. Among t he tested inhibitors, nordihydroguaiaretic acid and N-ethylmaleimide w ere more potent enhancers of cell dissociation than trifluoperazine. T hese results suggest that biosignaling pathways connected with lipoxyg enase activity as well as the level of intracellular sulfhydryl groups confer further stability to lectin-dependent cell aggregates. The sys tematic evaluation of inhibitors for defined activities is thus sugges ted as a tool to disclose the nature and the contribution of individua l signaling mechanisms to post-binding effects following lectin-initia ted cell contact formation.