thrombopoietin;
signal transduction;
inflammation;
interleukin;
8;
c-Mpl;
D O I:
10.1172/JCI119320
中图分类号:
R-3 [医学研究方法];
R3 [基础医学];
学科分类号:
1001 ;
摘要:
Thrombopoietin (TPO) regulates early and late stages of platelet formation as well as platelet activation, TPO exerts its effects by binding to the receptor, encoded by the protooncogene c-mpi, that is expressed in a large number of cells of hematopoietic origin, In this study, we evaluated the expression of c-Mp1 and the effects of TPO on human polymorphonuclear cells (PMN), We demonstrate that PMN express the TPO receptor c-Mp1 and that TPO induces STAT1 tyrosine phosphorylation and the formation of a serum inducible element complex containing STAT1, The analysis of biological effects of TrO an PMN demonstrated that TPO, at concentrations of 1-10 ng/ml, primes the response of PMN to n-formyl-met-leu-phe (FMLP) by inducing an early oxidative burst, TPO-induced priming on FMLP-stimulated PMN was also detected on the tyrosine phosphorylation of a protein with a molecular mass of similar to 25 kD. Moreover, we demonstrated that TPO by itself was able to stimulate, at doses ranging from 0.05 to 10 ng/ml, early release and delayed synthesis of interleukin 8 (IL-8), Thus, our data indicate that, in addition to sustaining megakaryacytopoiesis, TPO may have an important role in regulating PMN activation.