PRODUCTION AND METABOLISM OF PLATELET-ACTIVATING-FACTOR BY HUMAN BONE-MARROW CELLS

Platelet-activating factor (PAF) is a phospholipid mediator of inflamm ation present in the human bone marrow. Freshly isolated human mononuc lear bone marrow cells and marrow stromal cell cultures produced PAF u nder calcium ionophore (2 mu M) and LPS (10 mu g/ml) stimulation. By c ontrast, M-CSF (1000 U/ml), GM-CSF (100 ng/ml), IL1, IL3, IL6 and stem cell factor (10 ng/ml) did not stimulate PAF production. Marrow strom al cells produced 50-fold more PAF than freshly isolated mononuclear m arrow cells, suggesting that stromal cells might be the major source o f the human marrow-derived PAF. Mononuclear marrow cells and stromal c ell cultures metabolized PAF with 1-alkyl-2-acyl-glycerophosphocholine as the major metabolic product. PMSF and p-BPB decreased the cataboli sm of PAF by freshly isolated marrow cells, but not by stromal cell cu ltures. While stromal cells rather than haematopoietic progenitors mig ht be a major source of the human bone-marrow-derived PAF, both cell t ypes metabolize it, suggesting their putative role in the regulation o f PAF concentration in the human bone marrow.