Solid-phase immunoglobulins IgG and IgM activate macrophages with solid-phase IgM acting via a novel scavenger receptor a pathway.
Am J Pathol
; 181(1): 347-61, 2012 Jul.
Article
en En
| MEDLINE
| ID: mdl-22658487
ABSTRACT
IgG may accelerate atherosclerosis via ligation of proinflammatory Fcγ receptors; however, IgM is unable to ligate FcγR and is often considered vasculoprotective. IgM aggravates ischemia-reperfusion injury, and solid-phase deposits of pure IgM, as seen with IgM-secreting neoplasms, are well known clinically to provoke vascular inflammation. We therefore examined the molecular mechanisms by which immunoglobulins can aggravate vascular inflammation, such as in atherosclerosis. We compared the ability of fluid- and solid-phase immunoglobulins to activate macrophages. Solid-phase immunoglobulins initiated prothrombotic and proinflammatory functions in human macrophages, including NF-κB p65 activation, H(2)O(2) secretion, macrophage-induced apoptosis, and tissue factor expression. Responses to solid-phase IgG (but not to IgM) were blocked by neutralizing antibodies to CD16 (FcγRIII), consistent with its known role. Macrophages from mice deficient in macrophage scavenger receptor A (SR-A; CD204) had absent IgM binding and no activation by solid-phase IgM. RNA interference-mediated knockdown of SR-A in human macrophages suppressed activation by solid-phase IgM. IgM binding to SR-A was demonstrated by both co-immunoprecipitation studies and the binding of fluorescently labeled IgM to SR-A-transfected cells. Immunoglobulins on solid-phase particles around macrophages were found in human plaques, increased in ruptured plaques compared with stable ones. These observations indicate that solid-phase IgM and IgG can activate macrophages and destabilize vulnerable plaques. Solid-phase IgM activates macrophages via a novel SR-A pathway.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inmunoglobulina G
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Inmunoglobulina M
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Receptores Depuradores de Clase A
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Placa Aterosclerótica
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Activación de Macrófagos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Am J Pathol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido