Stem cell factor enhances IgE-mediated histamine and TNF-alpha release from dispersed canine cutaneous mast cells

Stem cell factor (SCF) the c-kit receptor ligand, plays a critical role in mast cell (MC) development and differentiation. In addition, SCF has recent ly been found to both modulate and induce MC activation. To investigate the effect of SCF on canine cutaneous MC function, we have characterized the a bility of SCF to modulate the release by mature canine MC of preformed (his tamine) and newly generated (TNF-alpha) mediators. Mature MC were isolated from skin and cultured in the absence or presence o f exogenous SCF (6 ng/ml) for up to 5 days and then challenged with anti-Ig E (1 mu g/ml) alone for 30) min or with a combination of SCF (50 ng/ml) and anti-IgE. SCF alone failed to trigger either histamine or TNF-alpha releas e at any time. However, we observed that SCF used as a co-stimulus signific antly potentiated histamine and TNF-alpha release in canine MC activated th rough Fc epsilon RI regardless of whether or not SCF was added to the mediu m during culturing. Thus, the mean histamine release (%) and TNF-alpha prod uction (pg/ml) were found to be significantly higher if cells were maintain ed in culture in SCF-supplemented medium compared with cells cultured in th e absence of exogenous SCE We also observed that MC responsiveness to immun ological stimulation increased with culture time, the percentage of histami ne released being higher in cells cultured for at least 3 days when compare d to freshly isolated MC. Taken together these findings suggest that canine skin MC releasability can be enhanced independently either through prolong ed incubation with SCF and/or through anti-IgE and SCF co-stimulation; (C) 2000 Elsevier Science B.V. All rights reserved.