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(Circulation. 2004;110:193-200.)
© 2004 American Heart Association, Inc.

Original Articles

Soluble Fibrin Is the Main Mediator of Staphylococcus aureus Adhesion to Platelets

Silke Niemann, MSc; Nicola Spehr, VMD; Hugo Van Aken, MD; Eberhard Morgenstern, MD; Georg Peters, MD; Mathias Herrmann, MD; Beate E. Kehrel, PhD

From the Department of Anaesthesiology and Intensive Care (S.N., N.S., H.V.A., B.E.K.) and the Institute for Medical Microbiology (G.P.), University Hospital Muenster, Muenster, Germany; and the Department of Anatomy and Cell Biology (E.M.) and Institute for Microbiology and Hygiene (M.H.), University of Saarland, Homburg/Saar, Germany.

Correspondence to Prof Dr Beate E. Kehrel, Department of Anaesthesiology and Intensive Care, Mendelstr 11, D-48149 Muenster, Germany. E-mail kehrel{at}uni-muenster.de

Received August 11, 2003; de novo received December 10, 2003; revision received March 16, 2004; accepted March 22, 2004.

Background— Infective endocarditis (IE) caused by Staphylococcus aureus is associated with significant morbidity and mortality rates. Platelets play a dual role as adhesive cells forming associates with bacteria as well as specialized inflammatory cells. The specific role of the various factors involved in bacteria-platelet association has not yet been fully elucidated.

Methods and Results— We observed a dramatic increase in the capability to bind S aureus when platelets were activated with thrombin (from 5% to 30%, P<0.001). To pinpoint platelet-binding sites involved in the interaction, platelets from knockout mice and from patients with selective inherited deficiency of membrane proteins or of granules were used. CD36, GPIIb/IIIa, and P-selectin were excluded as receptors for S aureus. Platelets from patients with -–storage pool disease and Gray platelet syndrome indicate the requirement of -granule contents. Platelet activation by ADP did not promote platelet–S aureus associate formation, although these platelets were covered with bound fibrinogen. Only small numbers of associates between fibrinogen-covered bacteria and ADP-activated platelets were observed. Formation of fibrin alone was also not sufficient to induce association. Only when fibrin formation and platelet activation occurred together were large numbers of associates formed (P<0.001). A potential receptor for fibrin on S aureus is clumping factor A. Addition of thrombospondin-1 to control platelets increased the number of associates (P=0.02).

Conclusions— Soluble fibrin but not fibrinogen is the main mediator of platelet–S aureus association. In addition, platelet activation and the release of -granule contents, particularly thrombospondin-1, is a requirement for platelet–S aureus association.

Key Words: platelets • endocardium • fibrin • infection

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