In:
The Journal of Immunology, The American Association of Immunologists, Vol. 175, No. 5 ( 2005-09-01), p. 2801-2806
Abstract:
Peptides originally derived from complement component C3a were earlier shown to inhibit the type I FcεR (FcεRI)-mediated degranulation of mucosal type mast cells. In the present study, we show that C3a7, a peptide with a natural sequence, and its modified derivative, C3a9, are powerful inhibitors of the above response of both serosal and mucosal type mastocytes. We demonstrate that these peptides inhibit FcεRI-induced membrane proximal events, suppress phosphorylation of the FcεRI β subunit, the protein tyrosine kinase Lyn, as well as the transient rise in free cytosolic Ca2+ level. The late phase of cellular response was also inhibited, as demonstrated by the reduced TNF-α secretion. Experiments using two independent methods provided evidence that the interaction site of complement-derived peptides is the FcεRI β-chain. This was further supported by fluorescence confocal microscopic colocalization and resonance energy transfer measurements. Taken together, these results suggest the presence of distinct “activating” and “inhibitory” motifs in the C3a sequence. Response to both is in balance under physiologic conditions. Furthermore, present data predict that such inhibitory peptides may serve as potent agents for future therapeutic intervention.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.175.5.2801
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2005
detail.hit.zdb_id:
1475085-5
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