title: Regulation of polymorphonuclear cell activation by thrombopoietin.
abstract: 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-mpl, that is expressed in a large number of cells of hematopoietic origin. In this study, we evaluated the expression of c-Mpl and the effects of TPO on human polymorphonuclear cells (PMN). We demonstrate that PMN express the TPO receptor c-Mpl and that TPO induces STAT1 tyrosine phosphorylation and the formation of a serum inducible element complex containing STAT1. The analysis of biological effects of TPO on 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 approximately 28 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 megakaryocytopoiesis, TPO may have an important role in regulating PMN activation.
authors.affiliation: Dipartimento di Medicina Interna, Università di Bologna, Italy.
authors.forename: M F
authors.initials: MF
authors.lastname: Brizzi
authors.forename: E
authors.initials: E
authors.lastname: Battaglia
authors.forename: A
authors.initials: A
authors.lastname: Rosso
authors.forename: P
authors.initials: P
authors.lastname: Strippoli
authors.forename: G
authors.initials: G
authors.lastname: Montrucchio
authors.forename: G
authors.initials: G
authors.lastname: Camussi
authors.forename: L
authors.initials: L
authors.lastname: Pegoraro
mesh_terms: D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects*; D010766:Phosphorylation; D011817:Rabbits; D050794:STAT1 Transcription Factor; D013481:Superoxides / Q000378:metabolism; D013926:Thrombopoietin / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D016209:Interleukin-8; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D013481:Superoxides; D014443:Tyrosine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013926:Thrombopoietin