Thrombopoietin-induced CXC chemokines, NAP-2 and PF4, suppress polyploidization and proplatelet formation during megakaryocyte maturation.
BACKGROUND
We previously reported that the expressions of two CXC chemokines, neutrophil activating peptide-2 (NAP-2) and platelet factor-4 (PF-4), were induced by megakaryocyte-specific cytokine thrombopoietin (TPO) in mouse bone marrow megakaryocytes. The roles of these chemokines on megakaryocyte maturation/differentiation processes, including polyploidization and proplatelet formation (PPF) remain unresolved.


RESULTS
NAP-2 and PF-4 suppressed the PPF of mature megakaryocytes freshly prepared from mouse bone marrow as well as that of the megakaryocyte progenitors, c-Kit+CD41+ cells, isolated from mouse bone marrow and cultured with TPO. NAP-2 and PF-4 inhibited polyploidization of c-Kit+CD41+ cells in the presence of TPO, and also inhibited the proliferation of c-Kit+CD41+ cells.


CONCLUSIONS
NAP-2 and PF-4 produced by TPO stimulation in megakaryocytes suppress megakaryocyte maturation and proliferation as a feedback control.
Oda
Masaaki
M
Laboratory of Molecular Cell Science, RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Kurasawa
Yasuhiro
Y
Todokoro
Kazuo
K
Nagata
Yuka
Y
D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D019743:Chemokines, CXC / Q000145:classification / Q000235:genetics / Q000502:physiology*; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D010978:Platelet Factor 4 / Q000502:physiology*; D011003:Ploidies; D013926:Thrombopoietin / Q000494:pharmacology
D019743:Chemokines, CXC; C446301:Cxcl7 protein, mouse; D010978:Platelet Factor 4; D013926:Thrombopoietin