Two-Phase Increment of Ca²⁺ Uptake, Intracellular Ca²⁺ Concentration, and Histamine Release Following Antigen Stimulation in Mouse Bone Marrow-Derived Mast Cells (BMMC)

Abstract

The relationship between the influx of Ca²⁺ into cells or cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and the histamine release following antigen stimulation in mouse bone marrow-derived mast cells (BMMC) was examined, and the results were compared with those from human lung mast cells (HLMC) and rat peritoneal mast cells (RPMC) in some experiments. Anaphylactic histamine release from BMMC as well as HLMC, but not that from RPMC, was dependent on the extracellular Ca²⁺. When BMMC were challenged by antigen following radioactive ⁴⁵Ca²⁺ addition, two phases of ⁴⁵Ca²⁺ influx into the cells were observed. The first phase, which was initiated and completed within 30 sec and 2 min, respectively, after antigen treatment, appeared to be related to anaphylactic histamine release. The second influx began 30 sec subsequent to the first one and lasted for at least 2 min, and this occurred after the completion of the histamine release; So far, it is not known how this second influx participates in the intracellular event(s). On the other hand, only one sustained elevation of [Ca²⁺]_i occurred that reached its maximum within 2 min after antigen stimulation. Following stimulation of BMMC with antigen in the absence of Ca²⁺, Ca²⁺ addition 1 to 5 min later time-dependently enhanced the histamine release, although the release was deteriorated by further extension of Ca²⁺ addition. In contrast, the releasability of HLMC was rapidly decreased. These results indicate that extracellular Ca²⁺ not only is prerequisite for anaphylactic histamine release from BMMC, but also may modulate the release and participate in some intracellular event(s) which has yet to be focused upon.