The c-kit receptor ligand functions as a mast cell chemoattractant

Abstract

Mast cells accumulate at sites of neovascularization, solid tumors, and many immune reactions. Such accumulation requires directed migration of mature mast cells or their precursors. The nature of the chemoattractants that regulate mast cell motility and the identity of the receptors that mediate the chemotactic response are poorly understood. We have tested the ability of stem cell factor (SCF), a mast cell growth factor, to stimulate mast cell migration. Our results show that SCF is a potent mast cell attractant that stimulates directional motility of both mucosal and connective tissue-type mast cells. The activity is potentiated by costimulation with interleukin-3 (IL-3), another mast cell chemoattractant. SCF, a known ligand for the c-kit tyrosine kinase receptor, was unable to stimulate motility in W42 mutant mast cells, which have a defective c-kit tyrosine kinase. However, W42 mast cells were still able to migrate in response to IL-3. These results show that SCF is a chemotactic factor as well as a growth factor and that the c-kit receptor can transduce signals leading to both cell proliferation and increased directional cell motility.

Characterization of a functional relationship between hepatocyte growth factor and mouse bone marrow-derived mast cells

“…3) and the motogenic effect of HGF did not involve a modulation of the adhesive function of β1 integrins (data not shown). In comparison, binding of c-kit ligand to the c-kit tyrosine kinase receptor has been shown to upregulate α4 and α5 integrin-mediated BMMC adhesion and migration [10,34,45,76]. In the present study, the effect of HGF on 4-week BMMC migration became detectable after 48 h stimulation (Fig.…”

Inflammatory mediators in naturally occurring rhinitis

“…Little is known in vivo about the dynamics of mast cell regranulation and of mast cell chemotaxis. A number of mast cell chemotactic agents have been proposed, including the cytokines IL-3 [31], TGF-b 1 [32] the chemokines IL-8 [33] and RANTES [34], the mast cell growth promoter, stem cell factor [35] and matrix components such as laminin and fibronectin [36,37]. Several of these chemotactic factors which have been proposed, often on the basis of murine studies, may not pertain to human disease, however, as human mast cells do not possess receptors for either laminin [38] or IL-3 [39,40].…”

Recent advances in the understanding of mastocytosis: the role of KIT mutations*

“…It is currently well-established that MC migration to peripheral tissues is also mediated by SCF/Kit signalling. SCF alone or in combination with interleukin-3, is a potent attractant for MC (Meininger et al, 1992). In addition, locally produced SCF may also exert an inhibitory effect on the chemotactic migration of MC induced by IgE-specific antigens, contributing to the accumulation of MC at the peripheral sites in allergic and non-allergic conditions (Sawada et al, 2005).…”