Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice

Faria-Neto, José Rocha; Chyu, Kuang‐Yuh; Li, Xiaojun; Dimayuga, Paul C.; Ferreira, Carmel; Yano, Juliana; Cercek, Bojan; Shah, Prediman K.

doi:10.1016/j.atherosclerosis.2005.11.033

Cited by 161 publications

(124 citation statements)

References 25 publications

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“…Indeed, immunization induced high titers of E06/T15 IgM and significantly reduced atherosclerosis (29). The atheroprotective property of anti-PC IgM was corroborated in a vein graft atherosclerosis model by Faria-Neto et al, in which they infused T15 IgM intravenously (30), and by Caligiuri et al, who demonstrated that immunizing apoE 2/2 mice with PC-KLH was atheroprotective (16). Furthermore, we (28,31) and others (32) have shown that E06 can bind to and block pro-inflammatory effects of PC containing OxPL, and this property undoubtedly also contributes importantly to the anti-inflammatory and anti-atherogenic properties of these oxidation-specific IgM.…”

Section: Nabs Recognize Oxidation-specific Epitopesmentioning

confidence: 85%

The role of innate immunity in atherogenesis

Hartvigsen

Chou

Hansen

et al. 2009

Journal of Lipid Research

124

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Lipid peroxidation is a common event in health and is greatly accelerated in pro-inflammatory settings such as hypercholesterolemia. Consequently, oxidation-specific epitopes are generated, which are pro-inflammatory and immunogenic, leading to both adaptive and innate responses. Because innate immune mechanisms use conserved germline pattern recognition receptors (PRRs) that are preformed and present at birth, it is not obvious why they should bind to such epitopes. In this review, we put forward the hypothesis that because oxidation-specific epitopes are ubiquitous in both health and disease, and because they in essence represent "danger signals," they constitute a class of pathogenassociated molecular patterns leading to the natural selection of multiple innate PRRs that target such epitopes. We suggest that apoptotic cells, and the blebs and microparticles released from such cells, which are rich in oxidation-specific epitopes and thus pro-inflammatory, constitute an endogenous set of selecting antigens. In turn, natural antibodies, scavenger receptors, and soluble innate proteins, such as pentraxins, all represent PRRs that target such epitopes. We discuss the evidence for this hypothesis and the consequences of such responses in health and disease, such as

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Section: Nabs Recognize Oxidation-specific Epitopesmentioning

confidence: 85%

The role of innate immunity in atherogenesis

Hartvigsen

Chou

Hansen

et al. 2009

Journal of Lipid Research

124

View full text Add to dashboard Cite

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“…Subsequent research has demonstrated that anti-PC aids in clearance of apoptotic cells (6,30) and prevents the formation of pathogenic foam cells in atherosclerosis by clearing oxidized low density lipoprotein (1). Murine studies with PC vaccination have shown strong beneficial effects on experimental atherosclerosis in vivo (11)(12)(13), and human epidemiology has consistently linked anti-PC insufficiency to cardiovascular events (14)(15)(16)(17). These findings in combination with earlier knowledge on the presence of T15 B cells in germ-free mice (20) has led to the formulation of a hypothesis that germlineencoded PC-reactive Abs produced by innate B1 cells fulfill an important housekeeping function in human physiology (8,10).…”

Section: Discussionmentioning

confidence: 99%

“…These results have lead scientists to hypothesize that anti-PC has an important housekeeping function in homeostasis (8)(9)(10). This understanding has been further cemented by animal studies (11)(12)(13) and several large epidemiological studies (14)(15)(16)(17), which have consistently demonstrated that humans with low levels of anti-PC are at elevated risk of cardiovascular disease. Furthermore, high levels of anti-PC are negatively associated with atherosclerosis development in humans (18).…”

Section: P Hosphorylcholine (Pc) Is a Classic T-independent Ag That Imentioning

confidence: 99%

Naturally Occurring Human Phosphorylcholine Antibodies Are Predominantly Products of Affinity-Matured B Cells in the Adult

Fiskesund

Stéen

Amara

et al. 2014

The Journal of Immunology

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Phosphorylcholine (PC) is a classic T-independent Ag that is exposed on apoptotic cells, oxidized phospholipids, and bacterial polysaccharides. Experimental as well as epidemiological studies have over the past decade implicated Abs against PC (anti-PC) as anti-inflammatory and a strong protective factor in cardiovascular disease. Although clinically important, little is known about the development of anti-PC in humans. This study was conceived to dissect the human anti-PC repertoire and generate human mAbs. We designed a PC-specific probe to identify, isolate, and characterize PC-reactive B cells from 10 healthy individuals. The donors had all mounted somatically mutated Abs toward PC using a broad variety of Ig genes. PC-reactive B cells were primarily found in the IgM+ memory subset, although significant numbers also were detected among naive, IgG+, and CD27+CD43+ B cells. Abs from these subsets were clonally related, suggesting a common origin. mAbs derived from the same donors exhibited equivalent or higher affinity for PC than the well-characterized murine T-15 clone. These results provide novel insights into the cellular and molecular ontogeny of atheroprotective PC Abs, thereby offering new opportunities for Ab-based therapeutic interventions.

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“…Mass spectra were measured with the LCT-Premier XE TOF Instrument controlled by MassLynx 4.1 mation, angiogenesis, and others. Importantly, molecules that inhibit oxidized phospholipid activity have therapeutic benefi ts in models of atherosclerosis, implying a causal role for oxidized phospholipids in atherogenesis (10)(11)(12)(13)(14).…”

Section: Lipid Extraction and Quantifi Cation By Hplc-msmentioning

confidence: 99%