Micro-concentration Lipopolysaccharide as a Novel Stimulator of Megakaryocytopoiesis that Synergizes with IL-6 for Platelet Production

Scientific Reports
Di WuQing Zhang

Abstract

Lipopolysaccharide (LPS) induces platelet activation and enhances platelet sensitivity to aggregation, which might alter platelet counts. We found that serial doses of micro-concentration LPS significantly increased the platelet count in mice treated with kanamycin, along with increased expression of IL-6 compared with IL-3 and TPO in megakaryocytes obtained from the mouse bone morrow following LPS administration. Furthermore, LPS at lower levels ranging plus IL-6 effectively stimulated CFU-MK formation and increased CD41 expression and megakaryocyte polyploidization. Meanwhile, there was a sustained rise in the percentage of reticulated platelets in the whole blood in response to low-dosage LPS combined with IL-6. In vivo experiments also demonstrated that the administration of LPS combined with IL-6 substantially enhanced the number of circulating platelets in normal and thrombocytopenic mice. Notably, the optimal LPS concentration in combination with IL-6 might be a novel stimulator of TLR4 and IL-6R expression in Dami cell lines, which initially occurs through TLR4-IL-6R crosstalk and then involves the activation of NF-κB and phosphorylation of p38 MAPK. These data suggest a new paradigm for the regulation of megakaryocytop...Continue Reading

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Citations

Jan 16, 2019·Journal of Leukocyte Biology·Pierre Cunin, Peter A Nigrovic
Sep 16, 2017·Immunologic Research·David J FieldCraig N Morrell
Feb 9, 2019·The Journal of Experimental Medicine·Alessandro MalaraAlessandra Balduini

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Methods Mentioned

BETA
PCR
FACS
transfections
transcription factor assay
flow cytometry

Software Mentioned

MNOVA
Cell Quest
Quantity One

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