Oxidation-specific epitopes are major targets of innate immunity in atherothrombosis

Barbara Bartolini Gritti; Christoph J. Binder

doi:10.5482/HAMO-14-11-0069

Hämostaseologie, Table of Contents

Hamostaseologie 2016; 36(02): 89-96
DOI: 10.5482/HAMO-14-11-0069

Review

Schattauer GmbH

Oxidation-specific epitopes are major targets of innate immunity in atherothrombosis

Oxidations-spezifische Epitope und angeborene Immunreaktionen in der Atherothrombose

Authors

Barbara Bartolini Gritti

¹Department of Laboratory Medicine, Medical University of Vienna, Austria
Christoph J. Binder

¹Department of Laboratory Medicine, Medical University of Vienna, Austria

Abstract

Zusammenfassung

Atherosklerose ist eine chronisch-entzündliche Erkrankung der Gefäßwände, die durch das Zusammenspiel von Dyslipidämie und vermehrtem oxidativen Stress verursacht wird. Die damit verbundene Lipidperoxidation führt zu einer Reihe von Abbauprodukten von Membranlipiden, sogenannten oxidations-spezifischen Epitopen (OSE). OSE finden sich in oxidierten Lipoproteinen und auf der Oberfläche absterbender Zellen, und ihre Fähigkeit inflammatorische und thrombogene Reaktionen auszulösen ist weithin bekannt. Jüngste Studien konnten zeigen, daß OSE spezifische Zielstrukturen für eine Reihe von zellulären und humoralen Rezeptoren des angeborenen Immunsystems darstellen. Dadurch kann das Immunsystem, metabolische Abbaubprodukte erkennen und wichtige physiologische “Haushaltsfunktionen” vermitteln, z.B. durch die kontrollierte Entsorgung abgestorbener Zellen und oxidierten Moleküle. So wurde gezeigt, daß natürliche IgM Antikörper mit Spezifität für OSE Mäuse vor der Entstehung atherosklerotischer Läsionen schützen. So können spezifische natürliche IgM Antikörper die pro-inflammatorischen und pro-thrombotischen Effekte von OSE neutralisieren, währenddessen niedrige Plasmaspiegel OSE-spezifischer IgM Antikörper mit einem erhöhten Risiko für Myokardinfarkt assoziiert sind. Schlussfolgerung: Das Verständnis der molekularen Komponenten und Mechanismen, die an diesem Prozess beteiligt sind, werden in Zukunft dazu beitragen, Personen mit einem erhöhten Risiko für Atherothrombose besser zu identifizieren und möglicherweise neue therapeutische Ansatzpunkte zu definieren.

Summary

Atherosclerosis is a chronic inflammatory disease of the vascular wall that results from disturbed lipoprotein metabolism and increased oxidative stress. A major consequence of this is lipid peroxidation, which generates a number of breakdown products of membrane lipids that form so called oxidation-specific epitopes (OSE). OSE have been documented in oxidized lipoproteins and on the surface of dying cells and circulating microparticles, and their ability to trigger robust pro-inflammatory and prothrombotic responses has been demonstrated extensively. Recent studies have identified specific OSE as major targets of both cellular and soluble pattern recognition receptors of the innate immune system, including innate natural IgM antibodies. This allows the immune system to identify metabolic waste and mediate important physiological house keeping functions, e.g. by promoting the removal of cellular debris and by neutralizing oxidized molecules. Indeed, innate B1 cells and B1 cell derived natural IgM with specificity for OSE have been shown to protect mice from the development of athero-sclerotic lesions. Moreover, OSE-specific natural IgM antibodies bind and neutralize the pro-inflammatory and pro-thrombotic effects of OSE, and low levels of OSE-specific IgM are associated with an increased risk for myocardial infarction. Conclusion: Understanding the molecular components and mechanisms involved in this process, will help identify individuals with increased risk for atherothrombosis and indicate novel points for therapeutic intervention.

Schlüsselwörter

Atherothrombose - Oxidiertes LDL - angeborene Immunität - natürliche IgM Antikörper

Keywords

Atherothrombosis - oxidized LDL - innate immunity - natural IgM antibodies

Full Text

References

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