STEM-CELL FACTOR, THE KIT-LIGAND, INDUCES DIRECT DEGRANULATION OF RATPERITONEAL MAST-CELLS IN-VITRO AND IN-VIVO - DEPENDENCE OF THE IN-VITRO EFFECT ON PERIOD OF CULTURE AND COMPARISONS OF STEM-CELL FACTOR WITH OTHER MAST CELL-ACTIVATING AGENTS

We report that stem-cell factor (SCF), the ligand of the receptor enco ded by the c-kit protooncogene, is a potent activator of degranulation of rat peritoneal mast cells in vitro and in vivo. Freshly isolated, purified mast cells were relatively unresponsive to SCF (4-500 ng/ml) but progressively acquired responsiveness to this agent, assessed as s erotonin (5-HT) release, during 48 hr culture in vitro. The cells show ed a similar kinetic pattern of acquisition of responsiveness to anti- IgE but responded fully to calcium ionophore A23187 or compound 48/80 regardless of time in culture. Acquisition of mast cell responsiveness to SCF or anti-IgE was not due to serum factors or to recovery from t he Percoll purification procedure. During culture, mast cell expressio n of the SCF receptor (SCFR) increased, and this may explain in part t he increased responsiveness to SCF. However, surface IgE expression re mained constant, and the increased responses to anti-IgE therefore mus t reflect changes in components of the secretion-coupling pathway that are activated subsequent to IgE cross-linking. The unresponsiveness o f freshly isolated peritoneal mast cells to SCF or anti-IgE does not r eflect a state of in vive unresponsiveness, as peritoneal mast cells d egranulated in vivo in response to these agents. We conclude that in t erms of their responsiveness to SCF or anti-IgE, cultured tissue mast cells may be more representative than freshly isolated mast cells of s ecretory function in vive, and therefore may be more appropriate for p hysiological or pharmacological studies of SCF- or IgE-dependent secre tory responses.