Regulation of polymorphonuclear cell activation by thrombopoietin

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.