Thrombocytopenia impairs host defense during murine Streptococcus pneumoniae pneumonia
F.E. van den Boogaard, M. Schouten, S.F. de Stoppelaar, J.J.T.H. Roelofs, X. Brands, M.J. Schultz, C. van 't Veer, T. van der Poll
Voorzitter(s): prof. dr. Y. Smulders, VUmc, Amsterdam & dr. Y.W.J. Sijpkens, Bronovo Ziekenhuis, Den Haag
Woensdag 22 april 2015
15:00 - 16:00u
in Auditorium 2
Categorieën: parallelsessie (case reports/research)
Parallel sessie: Parallelsessie 2: Case reports/research
Background:
Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. In patients, thrombocytopenia is correlated with an adverse outcome of pneumonia. Platelets can modulate the host response to infection in several ways, i.e. by facilitating clot formation, production of antimicrobial proteins and interaction with neutrophils. We studied the effect of thrombocytopenia during murine pneumococcal pneumonia.
Methods:
Pneumonia was induced in mice by intranasal inoculation of S. pneumoniae. Platelets were depleted by anti-mouse thrombocyte serum; controls received non-immunogenic serum. Mice were observed in a survival study or sacrificed after 24 or 48 hours for harvesting of bronchoalveolar lavage fluid (BALF), lungs, spleen and plasma. In separate studies mice were treated with the platelet P2Y12 receptor inhibitor clopidogrel or placebo.
Results:
Thrombocytopenic mice (platelet counts <1% of uninfected controls) showed a reduced survival during pneumococcal pneumonia (27% versus 75% amongst controls; p = 0.003), which was associated with higher bacterial loads in lungs, spleen, and blood. Thrombocytopenic mice showed enhanced coagulation activation (thrombin-antithrombin complexes) in plasma. Proinflammatory cytokine levels were higher in plasma but not in lungs of thrombocytopenic mice. Although clopidogrel treatment strongly prolonged the bleeding time, it did not impact on bacterial loads during pneumococcal pneumonia.
Conclusion:
Platelets play a protective role during pneumococcal pneumonia independent of their aggregation.
