DIRECT AND REVERSIBLE INHIBITION OF PLATELET FACTOR-4 ON MEGAKARYOCYTE DEVELOPMENT FROM CD34(-BLOOD CELLS - COMPARATIVE-STUDIES WITH TRANSFORMING GROWTH-FACTOR-BETA-1() CORD)

Mechanisms of the action of platelet factor 4 (PF4) on the growth of m egakaryocyte (MK) progenitor cells in CD34(+) cord blood (CB) cells we re studied in comparison with transforming growth factor beta 1 (TGF b eta 1). Development of MK from CD34(+) CB cells in both plasma clot cu lture and liquid culture was significantly inhibited by either purifie d human PF4 and by recombinant human TGF beta 1. Inhibition of MK colo ny formation by PF4 was reversible, because CD34(+) cells preincubated with PF4 could regenerate colonies after washing and replating into s econdary cultures. In contrast, TGF beta 1-preincubated CD34(+) cells gave rise to few colonies following replating. Moreover, incubation of CD34(+) cells with PF4 in liquid culture caused the increased number of both stem cell factor (SCF)-binding cells and CD34 antigen-bearing cells. In addition, PF4-preincubated CD34(+) cells exibited a higher p otential in MK colony formation in the presence of 5-fluorouracil (5FU ), These results demonstrate that both PF4 and TGF beta 1 inhibit MK d evelopment from CD34(+) CB cells by different mechanisms, and suggest that PF4, unlike TGF beta 1, exerts its inhibitory effect on the growt h of the target cells in a reversible manner which results in a preser vation of a more immature and 5FU-resistant cell population.