A granular variant of CD63 is a regulator of repeated human mast cell degranulation.
Allergy
; 65(10): 1242-55, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-20337613
ABSTRACT
BACKGROUND:
Mast cells are secretory immune cells whose degranulation can provoke acute allergic reactions. It is presently unclear, however, whether an individual mast cell can repeatedly degranulate or turns dysfunctional after a single antigen stimulus. This work thus aims to better define the mast cell life cycle, with particular focus on new target structures for therapeutic or diagnostic approaches in allergy.METHODS:
Monoclonal antibodies were raised against degranulated cord blood-derived human mast cells. A subset of these antibodies that exclusively recognized degranulated mast cells, but did not cross-react with quiescent mast cells or other hematopoietic cell types, became key reagents in subsequent experiments.RESULTS:
We identified a granular variant of tetraspanin CD63 as an exclusive molecular marker of degranulated human mast cells. Mutant analyses indicate that a cysteine cluster around residue C170 and protein glycosylation at residue N172 account for the antibody specificity. Here, we show that mast cells, which underwent an initial FcεRI-mediated degranulation, can be degranulated for at least another cycle in vitro. Repeated degranulation, however, requires an IgE/antigen stimulus that differs from the preceding one. Furthermore, the new variant-specific anti-CD63 antibodies effectively impair repeated cycles of mast cell degranulation.CONCLUSION:
Our findings indicate that mast cells are stable, multiple-use cells, which are capable of surviving and delivering several consecutive hits. Surface expression of the novel CD63 variant is a distinguishing feature of such primed cells. Reagents directed against this molecular hallmark may thus become valuable diagnostic and therapeutic agents.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Glicoproteínas de Membrana Plaquetaria
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Antígenos CD
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Degranulación de la Célula
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Mastocitos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Allergy
Año:
2010
Tipo del documento:
Article