Human Mast Cells Produce and Differentially Express Both Soluble and Membrane‐Bound Stem Cell Factor

Abstract

Stem cell factor (SCF), characterized as mast cell growth factor, is known to be produced by fibroblasts, keratinocytes and endothelial cells. Two different splice variants encode for either a soluble (SCF-1) or a membrane-bound (SCF-2) form. In order to explore whether mast cells themselves can produce SCF, we examined cultured cord blood (CBMC) and peripheral-blood-derived mast cells (PBMC), mast/basophil cell lines (HMC-1 and KU-812), and skin mast cells for SCF expression. On immunocytochemistry, cytoplasmatic SCF-reactivity was observed in HMC-1 cells, with additional cell membrane staining in KU-812, skin and cultured mast cells. Low amounts of SCF could be detected by ELISA in lysates of isolated and unstimulated mast cells and in supernatants of skin cells stimulated with anti-IgE or Ca-ionophore A23187. SCF mRNA was detected in all cells, although marked quantitative differences were observed among the various cell types. SCF-2 mRNA expression was low in HMC-1 cells while it was marked in skin mast cells, KU-812 cells, CBMC and PBMC. A time-dependent, increasing induction of both SCF forms was seen in CBMC and PBMC during culture. After stimulation with A23187 and phorbol myristate acetate, an up-regulation of SCF mRNA was noted in HMC-1 and KU-812 cells, without changes in the relationship of the two splice variants. The differential expression of SCF-specific mRNA splice variants in immature and mature human mast cells and the secretion of this molecule by these cells may play a role in autocrine stimulation, maintenance of survival and the differentiation of tissue mast cells.

Expression of SCF splice variants in human melanocytes and melanoma cell lines: potential prognostic implications

“…Since they also express c-Kit, cutaneous melanocytes are like mast cells potentially subject to autocrine regulation, in contrast to neutrophils and HL-60 cells which have been reported to express both splice variants of SCF, but not c-Kit (Ramenghi et al, 1994;Welker et al, 1999).…”

“…Using immunohistochemistry, Takahashi et al detected that few normal cutaneous melanocytes express SCF itself (Takahashi et al, 1995), and an SCF-dependent autocrine regulation of early melanogenesis has been discussed by Guo et al (1997). Expression of the splice variants has so far not been described in melanocytes, but both molecules have been detected in whole bone marrow, bone marrow stroma, peripheral blood neutrophils, human mast cells and HL-60 cell lines (Ramenghi et al, 1994;Welker et al, 1999). SCF as well as c-Kit have so far been demonstrated in various solid tumours and tumour cell lines (Turner et al, 1992;Cohen et al, 1994;Grabbe et al, 1994;Inoue et al, 1994), including malignant melanoma (Turner et al, 1992;Luo et al, 1995;Papadimitriou et al, 1995;Takahashi et al, 1995).…”

A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

“…SCF is produced and released by various cells, including fibroblasts, keratinocytes and endothelial cells [10,11]. It has also been reported that into two parts by the kinase insert domain [4,5,[10][11][12][13]. (b) sSCF is generated by cleavage of mSCF (220 or 248) [6-9, 14, 15].…”

Is there a role for mast cells in psoriasis?

“…Furthermore, SCF is increasingly upregulated in basal cell carcinoma and also in tumor cells [211]. Interestingly, even mast cells themselves can produce SCF [203,215]. The receptor for SCF, Kit, is a transmembrane tyrosine kinase receptor that is practically exclusively expressed by mast cells in the dermis and by melanocytes in the epidermis [67,73].…”