Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemokines are proinflammatory peptides regulating the functions of various hematopoietic cells. We have analyzed the effects of seven recombinant human (rh) chemokines (MCAF, RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine release from basophils (MCAF, 5 micrograms/ml: 26.9 +/- 3.4%; other chemokines: < 5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleukin-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (< 1 microgram/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n = 2), skin (n = 1), uterus (n = 3), or tonsils (n = 3), even when cells had been preincubated with the mast cell agonist SCF. The chemokines also failed to modulate the expression of activation antigens (CD11b/C3biR, CD25/IL-2R beta, CD63, IL-3R alpha, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils respond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.
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PMID:Differential response of human basophils and mast cells to recombinant chemokines. 754 Dec 56

We have tested the histamine releasing properties and priming abilities of a wide range of recombinant or purified cytokines and growth factors on the basophils of 20 subjects (10 atopic and 10 nonatopic). We found that monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), RANTES, human macrophage inflammatory protein-1 alpha and human inflammatory protein-1 beta, Connective tissue activating peptide III and Neutrophil Activating Peptide-2 (NAP-2) cause histamine release from basophils and are all members of the intercrine/chemokine family. MCAF/MCP-1 was as potent as anti-IgE or C5a and it is clearly the major contributor to histamine releasing factor activity. RANTES was the second major histamine releasing factor among the positive cytokines. Both MCAF/MCP-1 and RANTES are present in conditioned mononuclear cell media and can be separated using Mono Q anion exchange chromatography. We also demonstrated that RANTES has unusual chromatographic properties in spite of its isoelectric point of > 9.0 because it is largely found in peak-2 of the Mono Q column rather than peak-1 in which intercrines such as MCAF/MCP-1, IL-8, and connective tissue activating peptide III are found. All other cytokines and growth factors tested were negative, with the exception of IL-3, which caused histamine release in a subpopulation of subjects, and also primed basophils for release by anti-IgE. Other basophil primers for anti-IgE-dependent histamine release were IL-5, mast cell growth factor (c-kit ligand), and insulin-like growth factor II. Using specific neutralizing antibodies we have shown that MCAF/MCP-1, RANTES, and IL-3 contribute significantly to the activity found in mononuclear cell culture supernatants. Granulocyte-macrophage-CSF, IP-10, I-309, IL-7, IL-8, IL-9, IL-10, IL-11, IgE-binding factor, TNF-alpha, TGF-beta 1, fibroblast growth factor, epidermal growth factor, and endothelial cell growth factor were negative for direct histamine release and as primers of basophils. Our results indicate that cytokines belonging to the intercrine/chemokine family are major constituents of the activity known as "histamine releasing factor" found in MNC supernatants.
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PMID:Characterization of the human basophil response to cytokines, growth factors, and histamine releasing factors of the intercrine/chemokine family. 767 99