Human mast cells express stem cell factor

Zhang, Shaoli; Anderson, David F.; Bradding, Peter; Coward, William R.; Baddeley, S. M.; Macleod, J. D. A.; McGill, James; Church, Martin K.; Holgate, Stephen T.; Roche, William R.

doi:10.1002/(sici)1096-9896(199809)186:1<59::aid-path140>3.0.co;2-j

Cited by 108 publications

(69 citation statements)

References 35 publications

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“…SCF is a key factor influencing the survival, maturation, migration, and function of mast cells (15,19,20). In this study, SCF was shown to both initiate NF-B activation and enhance activation induced by TNF-␣ and anti-IgE.…”

Section: Discussionmentioning

confidence: 77%

NF-κB and TNF-α: A Positive Autocrine Loop in Human Lung Mast Cells?

Coward

Okayama

Sagara

et al. 2002

The Journal of Immunology

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The generation of cytokines, particularly TNF-α, by mast cells is crucial for the initiation of the allergic response. A key transcription factor involved in the synthesis of TNF-α is NF-κB. Using a mAb specific for the activated form of NF-κB, immunocytochemistry, confocal microscopy, and gel shift assays have been used in conjunction to localize this transcription factor to human lung mast cells and to study its activation. Activation of mast cells with stem cell factor (10 ng/ml) and anti-IgE (1 μg/ml) induced maximal activation of NF-κB at 4 and 2 h, respectively. In contrast, with TNF-α (5 ng/ml) maximal activation occurred within 15 min. Parallel falls in IκB were demonstrated. Confocal microscopy demonstrated the localization of the activated form of NF-κB to the nuclei of activated mast cells. NF-κB activation was verified using a gel shift assay. A supershift assay showed mast cell NF-κB to be composed primarily of p50 with smaller amounts of p65. No interaction with Abs for Rel-A, c-Rel, Rel-B, and p52 was seen. Immunocytochemistry and ELISAs showed TNF-α to be stored within mast cells and released into the extracellular environment following activation. The possible participation of TNF-α generated by mast cells in NF-κB activation by anti-IgE was investigated using a blocking Ab for TNF-α. The blocking Ab reduced NF-κB activation by anti-IgE by >50%, suggesting that the release of preformed mast cell-associated TNF-α acts as a positive autocrine feedback signal to augment NF-κB activation and production of further cytokine, including GM-CSF and IL-8.

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Section: Discussionmentioning

confidence: 77%

NF-κB and TNF-α: A Positive Autocrine Loop in Human Lung Mast Cells?

Coward

Okayama

Sagara

et al. 2002

The Journal of Immunology

Self Cite

123

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“…Similar to c-kit expression, different expression patterns were observed for SCF when mRNA and protein abundance were compared in colorectal mucosa specimens by quantitative realtime RT-PCR and immunohistochemistry. SCF is produced by many cell types including mast cells (41), fibroblasts, stromal cells (42), and endothelial cells (43). The relative content of these cells and of epithelial cells may be altered in adenomatous and neoplastic tissues compared to normal tissues.…”

Section: Discussionmentioning

confidence: 99%

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes

Bellone¹,

Smirne²,

Carbone³

et al. 2006

Int J Oncol

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Abstract. Autocrine/paracrine stimulation of KIT has been observed in colorectal carcinoma (CRC) cell lines. We investigated the expression of KIT and stem cell factor (SCF) in CRC in comparison with premalignant colon lesions and normal colonic mucosa to assess the prognostic and therapeutic relevance of this receptor/ligand system in CRC. Transcript levels of c-kit and the two SCF splicing variants were determined quantitatively by real-time RT-PCR using cDNA obtained from normal, premalignant and malignant snap frozen colon tissue specimens. Immunohistochemistry with specific anti-KIT and anti-SCF antibodies was performed on paraffin-embedded tissue sections in order to localize the relative protein expression in epithelial compartments. Approximately 10% of patients expressed KIT in their adenoma or primary tumor. The majority of KIT-positive carcinomas co-expressed SCF. Real-time RT-PCR showed expression of c-kit and SCF transcripts in all cDNA specimens examined. A significant association between the co-expression of KIT/SCF and a worse clinical outcome was found. In conclusion, KIT expression was observed in a proportion of premalignant and malignant colonic lesions, while it was virtually absent in normal colon mucosa. Moreover, the majority of KIT-positive carcinomas co-expressed SCF, suggesting the possibility of aberrant signaling by an autocrine loop, as confirmed by the negative prognostic value of this association. Therefore, in the subset of CRC patients with concomitant KIT/SCF expression, the activity of Imatinib mesylate, a selective inhibitor of specific tyrosine kinases including KIT, may be exploited in combination with standard therapy.

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“…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].…”

Section: Regulation Of Mast Cell Number and Activity In The Psoriaticmentioning

confidence: 99%

Is there a role for mast cells in psoriasis?

et al. 2008

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Mast cells have traditionally been considered as eVector cells in allergy but during the last decade it has been realized that mast cells are essentially involved in the mechanisms of innate and acquired immunity. Upon activation by anaphylactic, piecemeal degranulation or degranulation-independent mechanisms mast cells can secrete rapidly or slowly a number of soluble mediators, such as serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and growth factors. Mast cells can express cell surface co-stimulatory receptors and ligands, and they can express MHC class II molecules and thereby present antigens. These soluble factors and cell surface molecules can interact with other cells, such as endothelial cells, keratinocytes, sensory nerves, neutrophils, T cell subsets and antigen presenting cells which are essential eVectors in the development of skin inXammation. Besides promoting inXammation, mast cells may attempt in some circumstances to suppress the inXammation and epidermal growth but the regulation between suppressive and proinXammatory mechanisms is unclear. Psoriasis is characterized by epidermal hyperplasia and chronic inXammation where tryptase-and chymase-positive MC TC mast cells are activated early in the developing lesion and later the cells increase in number in the upper dermis with concomitant expression of cytokines and TNF superfamily ligands as well as increased contacts with neuropeptide-containing sensory nerves. Due to the intimate involvement of mast cells in immunity and chronic inXammation the role of mast cells in psoriasis is discussed in this review.

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Human mast cells express stem cell factor

Cited by 108 publications

References 35 publications

NF-κB and TNF-α: A Positive Autocrine Loop in Human Lung Mast Cells?

NF-κB and TNF-α: A Positive Autocrine Loop in Human Lung Mast Cells?

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes

Is there a role for mast cells in psoriasis?

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