Desensitization of IgE-mediated IL-4 release from human basophils.

Previous studies demonstrated marked differences in the time course of interleukin-4 (IL-4) and histamine release, implying different mechanisms of desensitization. To explore this possibility basophils were desensitized with anti-IgE antibody by treating the cells for various periods of time in the absence of extracellular calcium (Ca[e]). The basophil response following addition of Ca(e) was assessed by measuring IL-4 or histamine release by measuring the cytosolic calcium response ([Ca2+]i). The kinetics of desensitization for IL-4 and histamine release did not differ; 50% desensitization occurred at 37+/-8 and 29+/-16 min for IL-4 and histamine release, respectively. The kinetics of desensitization as assessed by the [Ca2+]i response was found to be biphasic; an initial enhancement of the [Ca2+]i response after 5-15 min of desensitization was followed by a rapid decrease so that by 30 min the amount of desensitization was equivalent to that observed for histamine release. Other than this initial period of enhanced calcium response, desensitization kinetics were unexpectedly similar for all measured endpoints. These results suggest that, during stimulation in the absence of Ca(e), there is a down-regulation process that influences all events on a similar time scale. Because the time scales for secretion of histamine, LTC4 or IL-4 or the [Ca2+]i response markedly differ (i.e., stimulation in the presence of Ca(e), these results also indicate that down-regulatory processes differ depending on the presence or absence of Ca(e).