Co-Chaired
by:
Michael A. Beaven, NHLBI
Juan Rivera,
NIAMS
Balcony A , Natcher
Conference Center
Mast cells are responsible
for a variety of inflammatory allergic disorders
that affect a large proportion of the population.
Mast cells are activated via the multimeric
immune receptor FceRI to initiate an array
of intracellular signals that include early
activation of Src kinases and Syk. Propagation
and integration of these signals are achieved
through the assembly of proteins into “signaling
complexes” that
lead to release of inflammatory mediators.
The intriguing question is whether the information
now available points to discrete therapeutic
targets for treatment of allergic disease
since current treatments are antisymptomatic
rather than suppressive, with the exception
of glucocorticoid therapy. In addition to
acquired hypersensitivity to allergens, there
is increasing evidence that mast cells play
a role in innate immune responses, probably
through toll-like receptors, against acute
bacterial infections where the immunosuppressive
actions of glucorticoids may be detrimental.
Another key receptor on mast cells is Kit.
The interactions of Kit with its ligand,
stem cell factor, are critical for mast cell
proliferation, survival, and biologic function.
Mutations in Kit are associated with mastocytosis,
a clonal disorder. Kit thus becomes a target
for treatment of mastocytosis through identification
of small molecular weight inhibitors of Kit
tyrosine kinase activity. The speakers will
address past and present developments in
all of the above topics. Program
Mast
Cells Take Their Toll
Henry Metzger, NIAMS
Uncovering New Complexities in FceRI Signaling
with Possible Therapeutic Implications
Juan
Rivera, NIAMS
The Essential Function of the Syk Protein
Tyrosine Kinase in Signaling from FceRI
Reuben Siraganian, NIDCR
Suppression of FceRI-mediated Signals
by Glucocorticoids and Potential Relevance
to Therapy
Michael A. Beaven, NHLBI
Mutations in Kit Related to Mastocytosis
and Mast Cell Signaling
Dean D. Metcalfe,
NIAID
Modulation of Mast Cell Function in Innate
immunity by Toll-like Receptors
Marianna
Kulka, NIAID |
