Desensitization of IL-4 secretion from mouse bone marrow-derived mast cells

Several recent findings indicate that mouse bone marrow-derived mast cells (BMMC) express RNA encoding interleukin-4 (IL-4) and secrete detectable amounts of IL-4 in response to cross-linking of Fc epsilon RI receptors, Fc gamma R receptors, or to ionomycin. We investigated the desensitization of BMMC from the view point of both IL-4 secretion and histamine release. In a desensitization protocol, the cells were challenged with an optimal concentration of antigen (10 ng/ml of DNP33-BSA) in the absence of calcium for various periods of time followed by addition of calcium to determine the loss in ability to release histamine or IL-4. In the context of histamine release, BMMC were desensitized completely in 45 min (T1/2 approximately 5 min). By contrast, in the context of IL-4 secretion, BMMC were only partly desensitized (52 +/- 5% of the control response) after 1 h of desensitization. A longer-term (2-6 h) desensitization of BMMC did not result in complete inhibition of IL-4 secretion (44 +/- 5% of control after 6 h). Northern blot analysis showed that IL-4 mRNA accumulation was decreased after a 1 h desensitization (37% +/- 14% of non-desensitized cells), suggesting that desensitization of IL-4 release results from a decrease in the amount of mRNA accumulation. These and other data support the view that the IgE-mediated signal transduction cascade has meditor-specific pathways that are independently regulated by homeostatic mechanisms within mast cells.