A NOVEL GPIB ALPHA BINDING PROTEIN ON STREPTOCOCCUS GORDONII INDUCES PLATELET ROLLING AT LOW SHEAR
Abstract number: P-W-358
Kerrigan1 S.W., Jacubovics2 N., Meade1 G., Jenkinson2 H., Cox1 D.
11Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland 22Oral Science, University of Bristol, Bristol, United Kingdom
How-to-cite Kerrigan SW, Jacubovics N, Meade G, Jenkinson H, Cox D. A NOVEL GPIB ALPHA BINDING PROTEIN ON STREPTOCOCCUS GORDONII INDUCES PLATELET ROLLING AT LOW SHEAR. J Thromb Haemost 2007; 5 Supplement 2: P-W-358
Introduction: Infective endocarditis is associated with considerable morbidity and mortality. Platelet adhesion is a critical event in the pathogenesis and dissemination of the infective process. Streptococcus gordonii is among the principle causative organisms of this disease. Hsa is a surface protein on S. gordonii previously shown to bind platelet GPIb a. Here we describe the functional role of Hsa in supporting platelet adhesion via GPIba.
Methods:S. gordonii DL-1 deficient in the Hsa gene, was generated by allelic exchange with an antibiotic resistance cassette. Experiments were recorded in real time and visualized using bright-field microscopy for a period of 8 minutes.
Results: Wildtype S. gordonii (DL1) supported platelet adhesion in the absence of plasma proteins. Pre-incubation of platelets with a GPIba antibody inhibited adhesion by 616% (p<0.001). Platelet adhesion to S. gordonii deficient in Hsa was reduced by 415% (p0.001). Wildtype S. gordonii bound to purified GPIba, however, the Hsa mutant adhered significantly less (93% of wildtype p0.001). We further investigated the interaction between GPIba and Hsa under shear. Upon commencement of shear (50s-1), platelets interacted with DL1 with a rolling fashion followed by firm adhesion. This adhesion was completely inhibited by addition of a GPIba antibody. When platelets were sheared over the immobilized S. gordonii Hsa mutant no interaction was observed. In addition, DL1 failed to interact with platelets at the higher shear rate of 500s-1.
Conclusions: Collectively, these results identify a unique direct interaction between S. gordonii Hsa and platelet GPIb a. This interaction occurs at static and low shear but not at high shear, which is in direct contrast to the interaction between vwf and GPIb a Furthermore, we propose that platelets roll across the S. gordonii via a GPIba - Hsa interaction. Following this a second more stable interaction firmly immobilizes the platelet, thereby facilitating the intravascular colonization of a septic plaque.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
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