The Stem Cell Factor, its Properties and Potential Role in the Airways

Kassel, Olivier; Silva, Carla Cristina da; Frossard, Nelly

doi:10.1006/pupt.2001.0304

Cited by 11 publications

(11 citation statements)

References 145 publications

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“…The reasons for this disparity are not known. This review will summarize the function and potential role of the mast cell growth factor SCF in the asthmatic airways containing large numbers of degranulated mast cells (for review, see [4]).…”

Section: Introductionmentioning

confidence: 99%

Stem cell factor expression, mast cells and inflammation in asthma

Silva¹,

Reber²,

Frossard³

2006

Fundamemntal Clinical Pharma

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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.

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Section: Introductionmentioning

confidence: 99%

Stem cell factor expression, mast cells and inflammation in asthma

Silva¹,

Reber²,

Frossard³

2006

Fundamemntal Clinical Pharma

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“…Mast cells characteristically express c-kit, and the ligand for this receptor, stem cell factor (SCF), induces chemotaxis (15), as well as other important effects such as proliferation, differentiation, and inhibition of apoptosis (for review, see ref. 16). …”

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confidence: 99%

Chemotactic action of prostaglandin E₂on mouse mast cells acting via the PGE₂receptor 3

Weller

Collington

Hartnell

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

119

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Mast cells are long-lived cells that are principally recognized for their effector function in helminth infections and allergic reactions. These cells are derived from pluripotential hematopoietic stem cells in the bone marrow that give rise to committed mast cell progenitors in the blood and are recruited to tissues, where they mature. Little is known about the chemotactic signals responsible for recruitment of progenitors and localization of mature mast cells. A mouse model was set up to identify possible mast cell progenitor chemoattractants produced during repeated allergen challenge in vivo. After the final challenge, the nasal mucosa was removed to produce conditioned medium, which was tested in chemotaxis assays against 2-wk murine bone marrow-derived c-kit ؉ mast cells (BMMC). A single peak of chemotactic activity was seen on reverse-phase HPLC with a retention time and electrospray mass spectrum consistent with prostaglandin E 2 (PGE2). This lipid was found to be a highly potent chemoattractant for immature (2-wk) and also mature (10-wk) BMMC in vitro. Fluorescently labeled 2-wk c-kit ؉ BMMC, when injected intravenously, accumulated in response to intradermally injected PGE2. Analysis using TaqMan showed mRNA expression of the PGE2 receptors 3 (EP3) and 4 (EP4) on 2-and 10-wk BMMC. Chemotaxis induced by PGE2 was mimicked by EP3 agonists, blocked by an EP3 receptor antagonist, and partially inhibited by a MAPKK inhibitor. These results show an unexpected function for PGE2 in the chemotaxis of mast cells.allergy ͉ eicosanoids ͉ migration

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“…We hypothesize that the KITLG polymorphisms, likely together with some other BPD‐predisposing genetic variants, influence the homing or other functions of mast cells and mast cell subtypes. KITLG polymorphisms could contribute to altered expression of Kit ligand or altered ratios of the membrane‐bound and soluble forms of the protein; different airway cells produce variable ratios of these two isoforms . The effects of minor alleles of common variants, such as those of the associating KITLG polymorphisms, could become detrimental under certain conditions that predispose infants to the disease (e.g., very preterm birth predisposing infants to adverse environment).…”

Section: Discussionmentioning

confidence: 99%

“…Kit ligand and its receptor play important roles in hematopoiesis and in mast cell development and function, and they are utilized in multiple signaling pathways . Kit ligand is the principal growth factor for mast cells; it influences mast cell homeostasis and functions in the production of proinflammatory cytokines and recruitment of fibroblasts . Kit ligand is expressed in various pulmonary cells and may play important roles in inflammatory lung diseases …”

Section: Introductionmentioning

confidence: 99%