Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo.

Abstract

SummaryStem cell factor (SCF), also known as mast cell growth factor, kit ligand, and Steel factor, is the ligand for the tyrosine kinase receptor (SCFtL) that is encoded by the c-kit proto-oncogene. We analyzed the effects of recombinant human SCF (r-hSCF, 5-50 btg/kg/day, injected subcutaneously) on mast cells and melanocytes in a phase I study of 10 patients with advanced breast carcinoma. A wheal and flare reaction developed at each r-hSCF injection site; by electron microscopy, most dermal mast cells at these sites exhibited extensive, anaphylactic-type degranulation. A 14-d course ofr-hSCF significantly increased dermal mast cell density at sites distant to those injected with the cytokine and also increased both urinary levels of the major histamine metabolite, methyl-histamine, and serum levels of mast cell 0rFive subjects developed areas of persistent hyperpigmentation at r-hSCF injection sites; by light microscopy, these sites exhibited markedly increased epidermal melanization and increased numbers of melanocytes. The demonstration that r-hSCF can promote both the hyperplasia and the functional activation of human mast cells and melanocytes in vivo has implications for our understanding of the role of endogenous SCF in health and disease. These findings also indicate that the interaction between SCF and its receptor represents a potential therapeutic target for regulating the numbers and functional activity of both mast cells and cutaneous melanocytes.

Inhibition of mast cells by interleukin‐10 gene transfer contributes to protection against acute myocarditis in rats

“…The concentration of c-kit ligand or SCF, which is known to induce differentiation, aggregation, growth and activation of mast cells [37][38][39][40][41], was reduced by IL-10 gene transfer when compared to that in the acute myocarditis group, as seen in the immunohistochemical staining. Therefore, IL-10 gene transfer may have prevented mast cell degranulation and decreased the growth and density of mast cells via these mechanisms.…”

A randomized phase 2 study of PBPC mobilization by stem cell factor and filgrastim in heavily pretreated patients with Hodgkin's disease or non-Hodgkin's lymphoma

“…The incidence of patients experiencing at least one adverse event, regardless of relationship to study drug, was similar for both treatment groups (SCF plus filgrastim group, 94%; filgrastim alone group, 84%). Injection site reactions, thought to be the result of local mast cell degranulation, 40 were the most frequently reported adverse events in the SCF plus filgrastim group, occurring in 84% of patients. These reactions were mild to moderate in severity; were primarily injection site erythema (59%), pruritus (24%) and urticaria (18%); and generally occurred within 24 h after the SCF injection and spontaneously resolved within 24 to 48 h.…”

Improving stem cell mobilization strategies: future directions

“…Despite the efficacy of SCF, its use is hindered by the infrequent occurrence of severe anaphylactoid reactions and the resultant need to closely monitor patients after SCF administration. 111 Although approved for use in Canada and New Zealand, ancestim is not currently available in the United States, 21 and it is seldom used in Europe because of the relatively high risk of side effects.…”