Stem cell factor induces eosinophil activation and degranulation: mediator release and gene array analysis.
Eosinophils are effector cells that play an important role in the damage induced by the allergic process by releasing inflammatory mediators and proteolytic factors after activation. Stem cell factor (SCF) is a primary cytokine involved in hematopoiesis and mast cell differentiation, proliferation, and activation. Studies have also indicated that SCF is directly involved in pathogenesis of allergic airway inflammation. In the present study, we examined the ability of SCF to activate murine eosinophils for increased mediator release and up-regulation of chemokines. Initial data demonstrated that eosinophils have significant levels of surface c-kit protein, SCF receptor. SCF-activated eosinophils degranulate and release eosinophil peroxidase and leukotriene C(4) in a dose-dependent manner. In addition, SCF was further shown to induce the release of CC chemokines, RANTES, macrophage-derived chemokine (MDC), macrophage inflammatory protein-1beta (MIP-1beta), and C10 from eosinophils. To identify the extent of SCF-induced activation of eosinophils, we also performed gene array analysis using an array containing 1153 genes related to inflammation, including cytokines and their receptors, growth factors, structural and cytoskeletal genes, signal transduction genes as well as several other classes related to immune/inflammatory responses. The gene analysis indicated that more than 150 genes were significantly up-regulated in eosinophils after SCF stimulation. The gene array results were verified using a quantitative real-time polymerase chain reaction analysis to identify the expression of several chemokine and chemokine receptor genes. Altogether, these studies indicate that SCF is a potent eosinophil degranulator and activator that may play a number of roles during an inflammatory/immune response.
Oliveira
Sandra H P
SH
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Taub
Dennis D
DD
Nagel
James
J
Smith
Robert
R
Hogaboam
Cory M
CM
Berlin
Aaron
A
Lukacs
Nicholas W
NW
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D019742:Chemokines, CC / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003594:Cytoplasmic Granules / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D047209:Eosinophil Peroxidase; D004802:Eosinophilia / Q000097:blood; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D018836:Inflammation Mediators; D017997:Leukotriene C4 / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010544:Peroxidases / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects* / Q000502:physiology; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012555:Schistosomiasis mansoni / Q000097:blood / Q000150:complications; D015398:Signal Transduction / Q000235:genetics; D019089:Stem Cell Factor / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D019742:Chemokines, CC; D016207:Cytokines; D003598:Cytoskeletal Proteins; D018836:Inflammation Mediators; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D017997:Leukotriene C4; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D019009:Proto-Oncogene Proteins c-kit