The role of cyclic AMP, calcium and filamentous actin in adenosine modulation of Fc receptor-mediated phagocytosis in human neutrophils.
Biochim Biophys Acta
; 1222(2): 249-56, 1994 Jun 30.
Article
em En
| MEDLINE
| ID: mdl-8031862
ABSTRACT
The role of cyclic AMP, calcium and filamentous actin (F-actin) content during adenosine modulation of Fc receptor (FcR)-mediated phagocytosis in adherent human neutrophils was investigated. Phagocytosis of IgG-opsonized yeast particles was found to be enhanced by pico- to nanomolar concentrations of adenosine or the A1-agonist N6-cyclopentyl-adenosine (CPA) but reduced by micromolar concentrations of adenosine or the A2-agonist 5'-N-ethylcarboxamidoadenosine (NECA). NECA, in the presence of the cAMP-specific phosphodiesterase inhibitor Ro 20-1724, increased the intracellular content of cAMP during phagocytosis. Ro 20-1724 potentiated the NECA-induced reduction of the phagocytic capacity. These observations indicate that cAMP elevations are involved in A2-receptor-mediated inhibition of phagocytosis. NECA, in the presence of Ro 20-1724, markedly enhanced the action polymerization associated with adhesion to the substrate and contact with the phagocytic prey. During advanced phagocytosis, however, the F-actin content reached levels clearly below those observed in control cells. This prolonged depolymerization phase correlated with the A2-receptor-induced cAMP elevation. Depletion of intracellular free calcium abolished the cAMP-elevating effects of NECA, and also completely abrogated the A1- and A2-receptor-mediated effects on phagocytosis. However, since NECA reduced the F-actin content even in Ca(2+)-depleted cells, A2-receptor-mediated inhibition of phagocytosis could not be directly coupled to changes in the overall content of F-actin. Our results indicate that adenosine modulates FcR-mediated phagocytosis in a calcium-dependent way, and does so through 'stimulatory' A1 and 'inhibitory' A2 receptors, and also that cAMP elevation is linked to the A2-receptor-induced inhibition of phagocytosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Fc
/
Adenosina
/
Cálcio
/
Actinas
/
AMP Cíclico
/
Neutrófilos
Limite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
1994
Tipo de documento:
Article
País de afiliação:
Suécia