La trombina modula de forma diferencial la respuesta inflamatoria aguda a Escherichia coli y Staphylococcus aureus en sangre total humana

Thrombin plays a central role in thromboinflammatory responses, but its activity is blocked in the common ex vivo human whole blood models, making an ex vivo study of thrombin effects on thromboinflammatory responses unfeasible. In this study, we exploited the anticoagulant peptide Gly-Pro-Arg-Pro (GPRP) that blocks fibrin polymerization to study the effects of thrombin on acute inflammation in response to Escherichia coli and Staphylococcus aureus Human blood was anticoagulated with either GPRP or the thrombin inhibitor lepirudin and incubated with either E. coli or S. aureus for up to 4 h at 37°C. In GPRP-anticoagulated blood, there were spontaneous elevations in thrombin levels and platelet activation, which further increased in the presence of bacteria. Complement activation and the expression of activation markers on monocytes and granulocytes increased to the same extent in both blood models in response to bacteria. Most cytokines were not elevated in response to thrombin alone, but thrombin presence substantially and heterogeneously modulated several cytokines that increased in response to bacterial incubations. Bacterial-induced releases of IL-8, MIP-1α, and MIP-1β were potentiated in the thrombin-active GPRP model, whereas the levels of IP-10, TNF, IL-6, and IL-1β were elevated in the thrombin-inactive lepirudin model. Complement C5-blockade, combined with CD14 inhibition, reduced the overall cytokine release significantly, both in thrombin-active and thrombin-inactive models. Our data support that thrombin itself marginally induces leukocyte-dependent cytokine release in this isolated human whole blood but is a significant modulator of bacteria-induced inflammation by a differential effect on cytokine patterns.

Resumen tomado de PubMed (NCBI) para el registro citado, en el idioma original. La versión de referencia es la de la publicación original.

El resumen se deja sin traducir para conservar la redacción original de los autores.

Sangre humana anticoagulada con GPRP (bloquea la polimerización de la fibrina) o lepirudina se incubó hasta 4 h con Escherichia coli o Staphylococcus aureus. La activación del complemento y de monocitos y granulocitos aumentó igual en ambos modelos, pero IL-8, MIP-1α y MIP-1β fueron mayores con GPRP, e IP-10, TNF, IL-6 e IL-1β con lepirudina. Bloquear C5 e inhibir CD14 redujo significativamente las citocinas. Según los autores, la trombina apenas las induce, pero modula diferencialmente la inflamación bacteriana.

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