Stem cell factor stimulates the chemotaxis, integrin upregulation, and survival of human basophils.

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.

Eotaxin but not MCP-3 induces eosinophil influx into nasal fluid in allergic patients.

BACKGROUND: Eotaxin and MCP-3 (CC chemokines), owing to their preferential action on eosinophils, seem to be the very importance in the patophysiology of allergic rhinitis and asthma. The purpose of this study was to examine the effect of intranasally administered eotaxin and MCP-3 after specific allergen priming on the influx of inflammatory cells and their soluble mediators into the nasal mucosa. METHODS: Eotaxin and MCP-3 have been applied intranasally at the increasing doses of 1, 5 and 10 microg to allergic patients after allergen priming. The 'nasal pool' technique was used. The cell count and biochemical parameters in nasal lavage were evaluated before 30 min, and 4 and 24 h after the challenge with chemokines. RESULTS: Both eotaxin and MCP-3 induced the increase in clinical 'score' lasting till 24 h. Eosinophil influx into nasal mucosa after provocation with eotaxin was also observed. The challenge with MCP-3 did not induce any significant changes in nasal lavage fluid. CONCLUSIONS: Eotaxin is likely to play an important role in the pathogenesis of allergic conditions in humans. MCP-3 did not induce inflammatory cell influx into nasal mucosa. The role of this chemokine in the pathogenesis of allergic inflammation is difficult to assess and requires further studies.