Micro-concentration Lipopolysaccharide as a Novel Stimulator of Megakaryocytopoiesis that Synergizes with IL-6 for Platelet Production.
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 megakaryocytopoiesis and platelet production via a synergistic effect of LPS and IL-6, which has the potential to be used for the design of new therapies.
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Di
D
Wu
Key Laboratory of Tropical &Subtropical Fishery Resource Application &Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute of CAFS, Guangzhou, China.
Jun
J
Xie
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Xuejun
X
Wang
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Bingcheng
B
Zou
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Yin
Y
Yu
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Tao
T
Jing
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Songmei
S
Zhang
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.|Institute of Sun Yat-Sen University in Shenzhen, Shenzhen, China.
Qing
Q
Zhang
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003114:Colony-Forming Units Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007377:Interleukin-3 / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D007612:Kanamycin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010976:Platelet Count; D011123:Polyploidy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D034061:Thrombopoiesis / Q000187:drug effects*; D013926:Thrombopoietin / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007377:Interleukin-3; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D051197:Toll-Like Receptor 4; D007612:Kanamycin; D013926:Thrombopoietin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases