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.


CONCLUSIONS
SCF might be an important selective modulator of basophil function through a phosphatidylinositol 3 kinase-dependent pathway.
Heinemann
Akos
A
Department of Experimental and Clinical Pharmacology, Medical University of Graz, Austria. akos.heinemann@meduni-graz.at
Sturm
Gunter J
GJ
Ofner
Martina
M
Sturm
Eva M
EM
Weller
Charlotte
C
Peskar
Bernhard A
BA
Hartnell
Adele
A
D001491:Basophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D039481:CD11b Antigen / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D054412:Chemokine CCL8; D019742:Chemokines, CC / Q000008:administration & dosage; D002630:Chemotactic Factors / Q000008:administration & dosage; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015936:Complement C5a / Q000008:administration & dosage; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D007377:Interleukin-3 / Q000008:administration & dosage; D019402:Macrophage Inflammatory Proteins / Q000008:administration & dosage; D018945:Monocyte Chemoattractant Proteins / Q000008:administration & dosage; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
C515456:CCL11 protein, human; C515453:CCL8 protein, human; D039481:CD11b Antigen; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D054412:Chemokine CCL8; D019742:Chemokines, CC; D002630:Chemotactic Factors; D016023:Integrins; D007377:Interleukin-3; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D019089:Stem Cell Factor; D015936:Complement C5a; D019009:Proto-Oncogene Proteins c-kit