Release of arachidonic acid by stimulation of opsonic receptors in human monocytes: the FcgammaR and the complement receptor 3 pathways.
The role of the opsonic receptors FcgammaR and CR3 on the release of arachidonic acid (AA) by human monocytes was studied using IgG-ovalbumin (OVA) equivalence immune complexes (IC), anti-OVA IgG bound to OVA-coupled latex beads, and C3bi-bound IC. Release of AA was produced by IC and latex-OVA beads bound to IgG, whereas binding of C3bi to IC inhibited the ability of IC to release AA. In contrast, coating of zymosan particles with C3bi enhanced AA release as compared with that produced by non-coated particles. Masking of C3bi on C3bi-bound IC by incubation with anti-C3 IgG resulted in the recovery of their ability to release AA, thereby suggesting that binding of C3b by IC reduces their flogogenic effects, whereas opsonization of microbial walls by complement may enhance their proinflammatory potential. The binding/uptake of opsonized zymosan particles was inhibited by anti-CR3 Ab and C3bi-bound IC, but not by beta-glucan, mannan, and anti-Toll-like receptor 2 Ab. These findings show that cooperative engagement of CR3 on both the lectin-like site involved in beta-glucan binding and the I-domain involved in C3bi binding, as it can be observed in the innate immune response, produces AA release, whereas the unique interaction of C3bi-bound IC with the I-domain of CR3, as it may occur in the adaptive immune response, diverts the IC lattice from a productive interaction with FcgammaR linked to AA release.
Fernández
Nieves
N
Unidad de Investigación Hospital Clínico Universitario, 47005-Valladolid, Spain.
Renedo
Marta
M
Alonso
Sara
S
Crespo
Mariano Sánchez
MS
D016718:Arachidonic Acid / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005936:Glucans / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D037102:Lectins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008351:Mannans / Q000737:chemistry; D009000:Monocytes / Q000378:metabolism*; D010047:Ovalbumin / Q000378:metabolism; D010587:Phagocytosis; D011134:Polysaccharides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017452:Receptors, IgG / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D013997:Time Factors; D015054:Zymosan / Q000737:chemistry
D039481:CD11b Antigen; D005936:Glucans; D037102:Lectins; D016177:Macrophage-1 Antigen; D008351:Mannans; D011134:Polysaccharides; D017452:Receptors, IgG; D011971:Receptors, Immunologic; C091196:opsonin receptor; D016718:Arachidonic Acid; D010047:Ovalbumin; C008247:laminaran; D015054:Zymosan