Soluble fibrin is the main mediator of Staphylococcus aureus adhesion to platelets.

Abstract

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 alpha-delta-storage pool disease and Gray platelet syndrome indicate the requirement of alpha-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 alpha-granule contents, particularly thrombospondin-1, is a requirement for platelet-S aureus association.

• Authors: Silke Niemann, Nicola Spehr, Hugo Van Aken, Eberhard Morgenstern, Georg Peters, Mathias Herrmann, Beate E Kehrel
• Journal: Circulation (Circulation) Vol. 110 Issue 2 Pg. 193-200 (Jul 13 2004) ISSN: 1524-4539 [Electronic] United States
• PMID: 15197141 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Coagulase
• Hirudins
• Oligopeptides
• Thrombospondin 1
• Adenosine Diphosphate
• glycyl-prolyl-arginyl-proline
• Fibrin
• Fibrinogen
• Ancrod
• Thrombin

Topics

• Adenosine Diphosphate (pharmacology)
• Ancrod (pharmacology)
• Animals
• Bacterial Adhesion (physiology)
• Blood Platelet Disorders (blood)
• Blood Platelets (microbiology, physiology)
• Coagulase (genetics, physiology)
• Cytoplasmic Granules (metabolism)
• Fibrin (physiology)
• Fibrinogen (pharmacology)
• Hirudins (pharmacology)
• Humans
• Mice
• Mice, Knockout
• Oligopeptides (pharmacology)
• Platelet Activation (drug effects)
• Protein Binding
• Staphylococcus aureus (genetics, physiology)
• Thrombin (pharmacology)
• Thrombospondin 1 (pharmacology)