A novel conditional platelet depletion mouse model reveals the importance of platelets in protection against Staphylococcus aureus bacteremia.
J Thromb Haemost
; 13(2): 303-13, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25418277
BACKGROUND: Platelets are critical cells for maintaining vascular hemostasis, but their activities in other processes are becoming apparent. Specifically, the ability of platelets to recognize and respond to infectious agents is an important area of investigation. To understand the physiologic roles of platelets in vivo, most researchers have used antibody-mediated platelet depletion, which has certain limitations. OBJECTIVE: To develop an optimal system with which to study the contribution of platelets to protection against S. aureus blood infection. METHODS: Here, we describe a novel experimental model of conditional platelet depletion based on the Cre-recombinase cell ablation system. With this technology, the simian diphtheria toxin receptor was expressed in platelet factor 4-positive cells (megakaryocytes and platelets). RESULTS: Systemic administration of diphtheria toxin every 48 h resulted in reduced platelet numbers that became undetectable after 6 days. Although platelets were depleted, no other blood cells were affected. With this newly developed model, the functional contributions of platelets to protection against Staphylococcus aureus bacteremia was examined. Platelet-depleted mice succumbed to infection more rapidly than wild-type mice, and had a significantly higher bacterial burden in kidneys, elevated levels of serum markers of kidney damage, and increased levels of cytokines indicative of septic shock. CONCLUSIONS: Here, we illustrate a new mouse model for conditional platelet depletion, and implicate platelets as important participants in the immune response to bacterial blood infections.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones Estafilocócicas
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Staphylococcus aureus
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Plaquetas
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Bacteriemia
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Factor de Crecimiento Similar a EGF de Unión a Heparina
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Thromb Haemost
Asunto de la revista:
HEMATOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido