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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4291-4297
CHEMOKINES
Stem cell factor induces eosinophil activation and degranulation:
mediator release and gene array analysis
Sandra H. P. Oliveira,
Dennis D. Taub,
James Nagel,
Robert Smith,
Cory M. Hogaboam,
Aaron Berlin, and
Nicholas W. Lukacs
From the Department of Pathology, University of
Michigan Medical School, Ann Arbor, and the Department of Immunology,
National Institute on Aging, Baltimore, MD.
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 C4 in a dose-dependent manner. In addition,
SCF was further shown to induce the release of CC chemokines, RANTES,
macrophagederived chemokine (MDC), macrophage inflammatory
protein-1 (MIP-1 ), 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.

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