Human Keratinocytes Release Mast Cell Differentiation Factors Other than Stem Cell Factor

Abstract

Besides stem cell factor (SCF), additional fibroblast-derived mast cell growth factors have previously been described. Since keratinocytes have also been shown to produce SCF, we have studied the ability of culture supernatants from the human HaCaT keratinocyte cell line to induce SCF-independent mast cell differentiation. The immature human mast cells of the HMC-1 line which express a mutant continuously activated SCF receptor were used as model target cells. Culture supernatants from differentiating keratinocytes (at day 11 of culture), and far less so those from proliferating keratinocytes (day 4 of culture), caused a marked, dose-dependent increase of histamine and tryptase in HMC-1 cells. This suggests that human HaCaT keratinocytes release mast cell differentiation factors other than SCF, to a degree related to their state of differentiation.

Granule Formation in NGF-Cultured Mast Cells Is Associated with Expressions of Pyruvate Kinase Type M2 and Annexin I Proteins

“…The expression of proteins modulating granule formation by HMC-1 cells may occur through NGF signaling, TrkA/ERK [1, 3, 16, 26, 27]. Our finding that the TrkA/ERK pathway is involved in HMC-1 (online suppl.…”

“…However, the HMC-1 cell line has the characteristics of immature mast cells, which contain low levels of histamine and FcεRI [41]. In general, the differentiation of mast cell progenitors requires the presence of SCF [3]. It is known, though, that SCF has no effect on the maturation and differentiation of HMC-1 cells, unlike other human mast cells, because HMC-1 contains mutated SCF [42].…”

“…It is known, though, that SCF has no effect on the maturation and differentiation of HMC-1 cells, unlike other human mast cells, because HMC-1 contains mutated SCF [42]. Instead of SCF, NGF is considered to be the most likely candidate to promote human mast cell growth and differentiation [3, 4, 11]. Moreover, there are reports that NGF induces mast cell differentiation via the TrkA/ERK signal pathway [16, 26, 27].…”

“…Although the HMC-1 cell line has several good features, it is not frequently used because it is an immature cell line. Therefore, several attempts have been made to enhance its mast cell characteristics [3, 4]. The results obtained show that nerve growth factor (NGF), known as a fibroblast- and keratinocyte-derived growth factor, is the most likely candidate for mediating human mast cell growth factor activities [3].…”

Mediators Produced by Airway Epithelial Cells Influence Proliferation and Differentiation of Immature Mast Cells

“…Recently, it was reported that keratinocytes release a mediator that induces differentiation o f HMC-1 cells [7], which may bear resemblance to the epi thelial product described here. Since HMC-1 cells possess a constitutively activated kit ligand receptor which makes proliferation of HMC-1 cells independent o f kit ligand (KL), the observed effects on proliferation of HMC-1 cells are probably not due to KL production by epithelial cells [8].…”