EFFECT OF PLATELET-ACTIVATING-FACTOR ON THE GROWTH OF HUMAN ERYTHROIDAND MYELOID CD34(+) PROGENITORS

WE have assessed the effect of platelet-activating factor (PAF), a bio logically active phospholipid present in the human marrow, on the grow th of human marrow and blood CD34(+) progenitors. While the metaboliza tion rate of PAF by CD34(+) cells is low (weak acetylhydrolase and acy lation processes) it is readily catabolized by the acetylhydrolase act ivity present in the growth medium (10% fetal calf serum + 10% 5637-co nditioned medium). Treatment of marrow CD34(+) cells with the non-meta bolizable PAF agonist C-PAF (1 nM to 100 nM) immediately before semi-s olid culture significantly (P < 0.01) decreased the number of BFU-E bu t not of CFU-GM colonies. Treatment of marrow or blood CD34(+) cells w ith C-PAF (10-100 nM) for 3 days in liquid medium before semi-solid cu lture significantly (P < 0.01) decreased the number of BFU-E and CFU-G M colonies. Treatment of blood CD34(+) cells with the two PAF receptor antagonists CV 3988 and BN 5202 (1 mu M) had no significant effect on the number of BFU-E and CFU-GM colonies suggesting no role of endogen ous PAF in these processes. These results show that exogenous PAF down regulates human erythropoiesis and myelopoiesis, a result that might b e of importance during inflammatory states.