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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Costimulation of dectin-1 and DC-SIGN triggers the arachidonic acid cascade in human monocyte-derived dendritic cells
Journal of Immunology, Volume 180, No. 8, Year 2008
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Description
Inflammatory mediators derived from arachidonic acid (AA) alter the function of dendritic cells (DC), but data regarding their biosynthesis resulting from stimulation of opsonic and nonopsonic receptors are scarce. To address this issue, the production of eicosanoids by human monocyte-derived DC stimulated via receptors involved in Ag recognition was assessed. Activation of FcγR induced AA release, short-term, low-grade PG biosynthesis, and IL-10 production, whereas zymosan, which contains ligands of both the mannose receptor and the human β-glucan receptor dectin-1, induced a wider set of responses including cyclooxygenase 2 induction and biosynthesis of leukotriene C 4 and IL-12p70. The cytosolic phospholipase A2 inhibitor pyrrolidine 1 completely inhibited AA release stimulated via all receptors, whereas the spleen tyrosine kinase (Syk) inhibitors piceatannol and R406 fully blocked AA release in response to immune complexes, but only partially blocked the effect of zymosan. Furthermore, anti-dectin-1 mAb partially inhibited the response to zymosan, and this inhibition was enhanced by mAb against DC-specific ICAM-3-grabbing nonintegrin (SIGN). Immunoprecipitation of DC lysates showed coimmunoprecipitation of DC-SIGN and dectin-1, which was confirmed using Myc-dectin-1 and DC-SIGN constructs in HEK293 cells. These data reveal a robust metabolism of AA in human DC stimulated through both opsonic and nonopsonic receptors. The FcyR route depends on the ITAM/Syk/cytosolic phospholipase A2 axis, whereas the response to zymosan involves the interaction with the C-type lectin receptors dectin-1 and DC-SIGN. These findings help explain the distinct functional properties of DC matured by immune complexes vs those matured by β-glucans. Copyright © 2008 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Valera, Isela
Spain, Valladolid
Csic-uva - Instituto de Biologia y Genetica Molecular Ibgm
Fernández, Nieves
Spain, Valladolid
Universidad de Valladolid, Facultad de Medicina
Trinidad, Antonio García
Spain, Valladolid
Csic-uva - Instituto de Biologia y Genetica Molecular Ibgm
Alonso, Sara
Spain, Valladolid
Csic-uva - Instituto de Biologia y Genetica Molecular Ibgm
Brown, Gordon D.A.
South Africa, Cape Town
University of Cape Town
Alonso, Andrés
Spain, Valladolid
Csic-uva - Instituto de Biologia y Genetica Molecular Ibgm
Crespo, Mariano Sánchez
Spain, Valladolid
Csic-uva - Instituto de Biologia y Genetica Molecular Ibgm
Statistics
Citations: 71
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.4049/jimmunol.180.8.5727
ISSN:
00221767
e-ISSN:
15506606