Solid-Phase Immunoglobulins IgG and IgM Activate Macrophages with Solid-Phase IgM Acting via a Novel Scavenger Receptor A Pathway

Boyle, Joseph J.; Christou, Ivy; Iqbal, M. Bilal; Nguyen, Aivi T.; Leung, Viola; Evans, Paul C.; Liu, Yu; Johns, Michael; Kirkham, Paul; Haskard, Dorian O.

doi:10.1016/j.ajpath.2012.03.040

Cited by 12 publications

(10 citation statements)

References 50 publications

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“…Furthermore, they showed the absence of FcmR in human monocytes and that it is not induced by M-CSF. Moreover, by showing that passively adsorbed IgM or their pentavalent Fc portion did not modulate TNF-a secretion induced by suboptimal amounts of HAGG, we definitively excluded that IgM could influence the IgG-mediated cytokine-inducing signaling events after binding to very recently proposed (51,52) or as yet undescribed receptors. Using the HUL IgM RF, we previously reported that the IC formed during the successive (instead of simultaneous) incubation of C-FBG with first the ACPA + IgG then the IgM RF did not result in increased TNF-a secretion (33).…”

Section: Discussionmentioning

confidence: 96%

IgM and IgA Rheumatoid Factors Purified from Rheumatoid Arthritis Sera Boost the Fc Receptor– and Complement-Dependent Effector Functions of the Disease-Specific Anti–Citrullinated Protein Autoantibodies

Anquetil

Clavel

Offer

et al. 2015

The Journal of Immunology

100

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Rheumatoid factors (RF) and the disease-specific anti–citrullinated protein autoantibodies (ACPA) coexist in the joints of rheumatoid arthritis (RA) patients where they probably contribute to synovitis. We investigated the influence of IgM and IgA RF on the FcR- and complement-dependent effects of ACPA immune complexes (ACPA-IC). When stimulated by ACPA-IC formed in the presence of IgM RF or IgA RF fractions purified from RA serum pools, M-CSF–generated macrophages skewed their cytokine response toward inflammation, with increases in the TNF-α/IL-10 ratio and in IL-6 and IL-8 secretion, and decreases in the IL-1Ra/IL-1β ratio. In the IgM RF-mediated amplification of the inflammatory response of macrophages, the participation of an IgM receptor was excluded, notably by showing that they did not express any established receptor for IgM. Rather, this amplification depended on the IgM RF-mediated recruitment of more IgG into the ACPA-IC. However, the macrophages expressed FcαRI and blocking its interaction with IgA inhibited the IgA RF-mediated amplification of TNF-α secretion induced by ACPA-IC, showing its major implication in the effects of RF of the IgA class. LPS further amplified the TNF-α response of macrophages to RF-containing ACPA-IC. Lastly, the presence of IgM or IgA RF increased the capacity of ACPA-IC to activate the complement cascade. Therefore, specifically using autoantibodies from RA patients, the strong FcR-mediated or complement-dependent pathogenic potential of IC including both ACPA and IgM or IgA RF was established. Simultaneous FcR triggering by these RF-containing ACPA-IC and TLR4 ligation possibly makes a major contribution to RA synovitis.

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Section: Discussionmentioning

confidence: 96%

IgM and IgA Rheumatoid Factors Purified from Rheumatoid Arthritis Sera Boost the Fc Receptor– and Complement-Dependent Effector Functions of the Disease-Specific Anti–Citrullinated Protein Autoantibodies

Anquetil

Clavel

Offer

et al. 2015

The Journal of Immunology

100

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“…However, splenectomy does not only affect B-cell biology (see the Monocytes section above). Regardless, solid phase IgG and IgM seem to activate macrophage populations in vitro [150]. Regardless, solid phase IgG and IgM seem to activate macrophage populations in vitro [150].…”

Section: Lymphocytes B-cellsmentioning

confidence: 99%

Immunological aspects of atherosclerosis

Woollard

2013

Clinical Science

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Cardiovascular disease is the leading cause of death in several countries. The underlying process is atherosclerosis, a slowly progressing chronic disorder that can lead to intravascular thrombosis. There is overwhelming evidence for the underlying importance of our immune system in atherosclerosis. Monocytes, which comprise part of the innate immune system, can be recruited to inflamed endothelium and this recruitment has been shown to be proportional to the extent of atherosclerotic disease. Monocytes undergo migration into the vasculature, they differentiate into macrophage phenotypes, which are highly phagocytic and can scavenge modified lipids, leading to foam cell formation and development of the lipid-rich atheroma core. This increased influx leads to a highly inflammatory environment and along with other immune cells can increase the risk in the development of the unstable atherosclerotic plaque phenotype. The present review provides an overview and description of the immunological aspect of innate and adaptive immune cell subsets in atherosclerosis, by defining their interaction with the vascular environment, modified lipids and other cellular exchanges. There is a particular focus on monocytes and macrophages, but shorter descriptions of dendritic cells, lymphocyte populations, neutrophils, mast cells and platelets are also included.

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“…In vitro, antibodies to CD16 blocked the vascular inflammation caused by IgG‐activated human macrophages (Boyle et al. ).…”

Section: Introductionmentioning

confidence: 99%

Leptin regulates CD16 expression on human monocytes in a sex-specific manner

et al. 2014

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Fat mass is linked mechanistically to the cardiovascular system through leptin, a 16 kDa protein produced primarily by adipocytes. In addition to increasing blood pressure via hypothalamic‐sympathetic pathways, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to atherosclerotic plaque development. These functions are also characteristics of CD16‐positive monocytes that have been implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of such CD16‐positive monocytes. Cells from 45 healthy men and women with age ranging from 20 to 59 years were analyzed. Circulating numbers of CD14++16++ monocytes, which are primary producers of TNFα, were positively related to plasma leptin concentrations (P < 0.0001), with a stronger correlation in men (P < 0.05 for leptin × sex interaction). In vitro, recombinant human leptin induced CD16 expression in a dose‐related manner (P = 0.02), with a stronger influence on monocytes from men (P = 0.03 for leptin × sex interaction). There were no sex‐related differences in total leptin receptor expression on any monocyte subtypes, relative expression of long versus short isoforms of the receptor, or soluble leptin receptor concentrations in the plasma. The number of circulating CD14+16++ monocytes, which preferentially migrate into nascent plaques, was positively related to systolic blood pressure (R = 0.56, P = 0.0008) and intima‐media thickness (R = 0.37, P = 0.03), and negatively related to carotid compliance (R = −0.39, P = 0.02). These observations indicate that leptin promotes the development of CD16‐positive monocyte populations in a sex‐specific manner and that these subpopulations are associated with diminished vascular function.

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Solid-Phase Immunoglobulins IgG and IgM Activate Macrophages with Solid-Phase IgM Acting via a Novel Scavenger Receptor A Pathway

Cited by 12 publications

References 50 publications

IgM and IgA Rheumatoid Factors Purified from Rheumatoid Arthritis Sera Boost the Fc Receptor– and Complement-Dependent Effector Functions of the Disease-Specific Anti–Citrullinated Protein Autoantibodies

IgM and IgA Rheumatoid Factors Purified from Rheumatoid Arthritis Sera Boost the Fc Receptor– and Complement-Dependent Effector Functions of the Disease-Specific Anti–Citrullinated Protein Autoantibodies

Immunological aspects of atherosclerosis

Leptin regulates CD16 expression on human monocytes in a sex-specific manner

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