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Solid-phase immunoglobulins IgG and IgM activate macrophages with solid-phase IgM acting via a novel scavenger receptor a pathway.

ABSTRACT: IgG may accelerate atherosclerosis via ligation of proinflammatory Fc? receptors; however, IgM is unable to ligate Fc?R 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-?B 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 (Fc?RIII), 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.

SUBMITTER: Boyle JJ

PROVIDER: S-EPMC5691330 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Solid-phase immunoglobulins IgG and IgM activate macrophages with solid-phase IgM acting via a novel scavenger receptor a pathway.

Boyle Joseph J JJ Christou Ivy I Iqbal M Bilal MB Nguyen Aivi T AT Leung Viola W Y VW Evans Paul C PC Liu Yu Y Johns Michael M Kirkham Paul P Haskard Dorian O DO

The American journal of pathology 20120530 1

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 abil ...[more]

PMID: 22658487

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Dataset Information

Solid-phase immunoglobulins IgG and IgM activate macrophages with solid-phase IgM acting via a novel scavenger receptor a pathway.

Publications

Solid-phase immunoglobulins IgG and IgM activate macrophages with solid-phase IgM acting via a novel scavenger receptor a pathway.

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