Lactoferrin inhibits platelet production from human megakaryocytes in vitro

The mechanism of megakaryopoiesis, proplatelet formation (PPF) and platelet (PLT) production is not fully elucidated. Lactoferrin (LF) has been reported to have many biological functions including cell proliferation and differentiation, and the LF receptor is present on megakaryocytic cells. In the present study, we examined the effect of human LF (hLF) on PLT production from primary megakaryocytes (MKs). At first, we developed a PLT production system derived from human CD34(+) cells by thrombopoietin (TPO) stimulation. Because the number of proplatelets, PLTs and CD41(+) MKs was remarkebly increased after day 5, we employed the TPO-induced CD34(+) cells on day 5. Then, the effect of hLF on PLT production from human primary MKs was examined. In the range of 3-30 mu g/ml, hLF significantly inhibited PLT production up to about 60%. However, it did not significantly change the intensity of CD41 expression in MKs and the ploidy of MKs. In addition, it did not inhibit MK progenitors. These results suggest that LF directly inhibits PLT production from matured MKs, but does not inhibit megakaryopoiesis, including proliferation/maturation processes.