Stem cell factor expression, mast cells and inflammation in asthma

Abstract

The Kit ligand SCF or stem cell factor (SCF) is a multipotent growth factor, acting as an important growth factor for human mast cells. SCF induces chemotaxis and survival of the mast cell, as well as proliferation and differentiation of immature mast cells from CD34(+) progenitors. Additionally, SCF enhances antigen-induced degranulation of human lung-derived mast cells, and induces a mast cell hyperplasia after subcutaneous administration. SCF expression increases in the airways of asthmatic patients, and this is reversed after treatment with glucocorticoids. A role for SCF may thus be hypothesized in diseases associated with a local increase in the number and/or activation of mast cells, as occurring in the airways in asthma. SCF will be reviewed as a potential therapeutic target in asthma, to control the regulation of mast cell number and activation. We here report the main pathways of SCF synthesis and signalling, and its potential role on airway function and asthma.

Mesenchymal Stem Cells Require MARCKS Protein for Directed Chemotaxis In Vitro

“…Interestingly, SCF, which has been speculated to act as a chemoattractant for mesenchymal cells in vivo (22), did not induce chemotaxis by BM-MSCs. Inasmuch as SCF is a potent factor in inflammatory cell attraction and maintenance of lung airway inflammation (22,35), these findings were surprising. SCF also did not affect MARCKS phosphorylation, providing additional evidence that phosphorylation of MARCKS is an important component of stem cell migration.…”

Expression of ADAMs (“a disintegrin and metalloprotease”) in the human lung

“…Not only ADAM33 [32] but also ADAM8 [33], ADAM9 [34], ADAM17 [35,36], and ADAM19 [20] are capable of shedding of c-kit ligand, also known as stem cell factor (SCF). SCF plays, apart from its main role as hemopoietic growth factor, a role in recruitment and in maturation of mast cell progenitors [37], sustaining the survival and maintaining phenotypic properties of mast cells in mucosal tissues [38,39]. Furthermore, SCF may play a role in eosinophil migration and/or retention in activated tissue compartments [31], given its expression on human peripheral blood cells.…”

The IL-33/ST2 axis: Role in health and disease

“…Stem cell factor (SCF) is the classical c-Kit ligand and is critical for mast cell growth, maturation and survival [56]. Stimulation of mast cells with SCF is necessary for IL-33-induced IL-6 production through the direct interaction between c-Kit and ST2L [55].…”