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-Chymase Reduces IgE Recognition of Birch Pollen Profilin by Cleaving Antibody-Binding Epitopes1
*
Cardiovascular Research Institute and
Department of Medicine, University of California, San Francisco, CA 94143
In sensitized individuals birch pollen induces an allergic response
characterized by IgE-dependent mast cell degranulation of mediators,
such as 
-chymase and other serine proteases. In birch and other
plant pollens, a major allergen is profilin. In mammals, profilin
homologues are found in an intracellular form bound to cytoskeletal or
cytosolic proteins or in a secreted form that may initiate signal
transduction. IgE specific to birch profilin also binds human profilin
I. This cross-reactivity between airborne and endogenous proteins may
help to sustain allergy symptoms. The current work demonstrates that
cultured mast cells constitutively secrete profilin I, which is
susceptible to degranulation-dependent proteolysis. Coincubation of
chymase-rich BR mastocytoma cells with
Ala-Ala-Pro-Phe-chloromethylketone (a chymase inhibitor) blocks
profilin cleavage, which does not occur in degranulated HMC-1 mast
cells, which are rich in tryptase, but chymase deficient. These data
implicate chymase as the serine protease cleaving secreted mast cell
profilin. Sequencing of chymase-cleaved profilins reveals hydrolysis at
Tyr6-Val7 and
Trp35-Ala36 in birch profilin and at
Trp32-Ala33 in human profilin, with all sites
lying within IgE-reactive epitopes. IgE immunoblotting studies with
sera from birch pollen-allergic individuals demonstrate that cleavage
by chymase attenuates binding of birch profilin to IgE. Thus,
destruction of IgE-binding epitopes by exocytosed chymase may limit
further mast cell activation by this class of common plant allergens,
thereby limiting the allergic responses in sensitized
individuals.
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