Regulation of polymorphonuclear cell activation by thrombopoietin

被引:27
作者
Brizzi, MF
Battaglia, E
Rosso, A
Strippoli, P
Montrucchio, G
Camussi, G
Pegoraro, L
机构
[1] UNIV TURIN,DIPARTIMENTO MED INTERNA,I-10126 TURIN,ITALY
[2] UNIV TURIN,DIPARTIMENTO FISIOPATOL CLIN,I-10126 TURIN,ITALY
[3] UNIV BOLOGNA,CTR INTERDIPARTIMENTALE RIC GIORGIO PRODI,IST ISTOL & EMBRIOL,BOLOGNA,ITALY
[4] UNIV PAVIA,FAC MED 2,IST MED & SANITA PUBB,VARESE,ITALY
关键词
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.
引用
收藏
页码:1576 / 1584
页数:9
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