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Heinemann, A; Sturm, GJ; Ofner, M; Sturm, EM; Weller, C; Peskar, BA; Hartnell, A.
Stem cell factor stimulates the chemotaxis, integrin upregulation, and survival of human basophils.
J ALLERG CLIN IMMUNOL. 2005; 116: 820-826.
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Autor/innen der Med Uni Graz:
Heinemann Akos
Peskar Bernhard
Sturm Eva
Sturm Gunter
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Abstract:
BACKGROUND: Little is known about the mechanisms that regulate the selective recruitment of basophils to sites of allergic inflammation. OBJECTIVE: Here we examine the role of stem cell factor (SCF) in the regulation of basophil function. METHODS: Human basophils were isolated from peripheral blood, and their migration was investigated in chemotaxis assays. Apoptosis was detected by means of annexin V and propidium iodide staining. The expression of cell-surface molecules was measured by means of flow cytometry. RESULTS: SCF amplified the chemotactic responsiveness of human peripheral blood basophils to the chemoattractants eotaxin, monocyte chemotactic protein 2 and macrophage inflammatory protein 1alpha, and C5a, without being chemotactic or chemokinetic by itself. SCF synergized with chemoattractants in causing basophil upregulation of the integrin CD11b, and this effect was inhibited by a c-kit antibody, the tyrosine kinase inhibitor imatinib mesylate (STI-571), and a phosphatidylinositol 3 kinase inhibitor but not by inhibitors of p38 mitogen-activated protein kinase or mitogen-activated protein kinase/extracellular signal-regulated kinase kinase. Basophils bound fluorescence-labeled SCF and expressed its receptor, c-kit, which was markedly upregulated in culture for 24 to 48 hours in the presence of IL-3. Moreover, SCF prolonged basophil survival in concert with IL-3 by delaying apoptosis. These effects of SCF were selective for basophils because chemotaxis and CD11b upregulation of eosinophils or neutrophils were unchanged. CONCLUSION: SCF might be an important selective modulator of basophil function through a phosphatidylinositol 3 kinase-dependent pathway.
Find related publications in this database (using NLM MeSH Indexing)
Antigens, CD11b - metabolism
Basophils - cytology
Cell Survival - drug effects
Chemokines, CC - administration and dosage
Chemotactic Factors - administration and dosage
Chemotaxis, Leukocyte - drug effects
Complement C5a - administration and dosage
Drug Synergism - administration and dosage
Humans - administration and dosage
In Vitro - administration and dosage
Integrins - metabolism
Interleukin-3 - administration and dosage
Macrophage Inflammatory Protein-1 - administration and dosage
Monocyte Chemoattractant Proteins - administration and dosage
Proto-Oncogene Proteins c-kit - metabolism
Research Support, Non-U.S. Gov't - metabolism
Signal Transduction - drug effects
Stem Cell Factor - administration and dosage
Up-Regulation - drug effects

Find related publications in this database (Keywords)
basophils
chemoattractants
allergy
stem cell factor
c-kit
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