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The role of stem cell factor (c-kit ligand) and inflammatory cytokines in
pulmonary mast cell activation
NW Lukacs, SL Kunkel, RM Strieter, HL Evanoff, RG Kunkel, ML Key and DD Taub
Department of Pathology, Division of Pulmonary and Critical Care,
University of Michigan Medical School, Ann Arbor, MI USA.
Mast cells play a critical role in allergic airway responses via IgE-
specific activation and release of potent inflammatory mediators. In the
present study, we have isolated and characterized primary mast cell lines
derived from the upper airways of normal mice. The primary mast cell lines
were grown and maintained by incubation with interleukin-3 (IL-3) and stem
cell factor (SCF) and shown to be c-kit (SCF receptor) positive by flow
cytometry. Subsequently, we examined the proliferation of both airway and
bone marrow derived mast cell lines in response to inflammatory and
hematopoietic cytokines, including SCF, IL-1, IL-3, interferon-gamma, IL-4,
and IL-10. The results from the pulmonary mast cell lines were compared
with those from bone marrow derived mast cells. Pulmonary mast cell lines
were capable of proliferating in response to IL-3, IL-4, IL-10, and SCF,
whereas the combination of SCF with the other cytokines did not increase
the response over SCF alone. In contrast, the bone marrow-derived mast
cells proliferated strongest to SCF or IL-3, but only modestly to IL-4 and
IL-10. Furthermore, the combination of SCF with IL-3, but not the other
cytokines, exhibited an increase in bone marrow-derived mast cell
proliferation. Cytokine- specific stimulation of histamine release in the
airway-derived and bone marrow-derived mast cells showed parallel results.
SCF was the only cytokine shown to induce substantial histamine release.
However, when certain nonhistamine releasing cytokines were combined with
SCF, a synergistic increase in histamine release was induced in upper
airway, but not bone marrow-derived mast cells. The results of these
studies suggest that cytokines differentially modulate induction of
proliferation and degranulation of bone marrow and upper airway-derived
mast cells and may further indicate a cytokine activational cascade in
tissue mast cells.
Volume 87,
Issue 6,
pp. 2262-2268,
03/15/1996
Copyright © 1996 by The American Society of Hematology
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