Local complement activation triggers neutrophil recruitment to the site of thrombus formation in acute myocardial infarction

Klaus Distelmaier; Christopher Adlbrecht; Johannes Jakowitsch; Susanne Winkler; Daniela Dunkler; Christopher Gerner; Oswald Wagner; Irene M. Lang; Markus Kubicek

doi:10.1160/TH09-02-0103

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(03): 564-572
DOI: 10.1160/TH09-02-0103

Platelets and Blood Cells

Schattauer GmbH

Local complement activation triggers neutrophil recruitment to the site of thrombus formation in acute myocardial infarction

Klaus Distelmaier

¹Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria

,

Christopher Adlbrecht

¹Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria

,

Johannes Jakowitsch

¹Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria

,

Susanne Winkler

¹Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria

,

Daniela Dunkler

²Section of Clinical Biometrics, Core Unit for Medical Statistics and Informatics, Medical University of Vienna, Vienna, Austria

,

Christopher Gerner

³Department of Internal Medicine I, Division of Cancer Research, Medical University of Vienna, Vienna, Austria

,

Oswald Wagner

⁴Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria

,

Irene M. Lang^*

¹Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria

,

Markus Kubicek^*

⁴Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria

› Author Affiliations

Abstract

Summary

Atherosclerotic plaque rupture with subsequent mural thrombus formation is considered the main event compromising epicardial flow in acute myocardial infarction (AMI). However, the precise mechanisms underlying acute coronary occlusion are unknown.

We compared the proteomic profiles of systemic plasma and plasma derived from the site of thrombus formation of patients with AMI by two-dimensional gel electrophoresis and ELISA. We identified a local activation of the complement system, with selective accumulation of the complement activator Creactive protein (CRP) and the downstream complement effectors C3a and C5a. CRP in coronary thrombus co-localised with C1q and C3 immunoreactivities, suggesting classical complement activation. In vitro, coronary thrombus derived plasma enhanced neutrophil chemotaxis in a C5a dependent fashion. In vivo, neutrophil accumulation at the site of thrombus formation paralleled the time delay from symptom onset to first balloon inflation or aspiration, and was correlated with C5a and enzymatic infarct size. We present the first direct evidence for localised complement activation in acute coronary thrombi. Our data indicate that local complement effectors amplify the vascular occlusion process in AMI by enhanced neutrophil recruitment.

Keywords

Acute myocardial infarction - complement - neutrophils - proteomics - thrombosis

Full Text

References

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