PAF AND HEMATOPOIESIS .8. BIOSYNTHESIS AND METABOLISM OF PAF BY HUMANBONE-MARROW STROMAL CELLS

Human bone marrow stromal cells were studied for their ability to synt hesize and to metabolize platelet-activating factor (PAF), a lipidic c ompound with potent immunoregulatory properties. When stimulated with 2 mu M calcium ionophore for 60 minutes, cultures of stromal cells inc reased their PAF production (3.52 +/- 0.91 ng/1x10(6) cells) compared with controls (0.82 +/- 0.13 ng/1x10(6) cells). Addition of exogenous lyse PAF (100 nM) and acetyl-CoA (100 mu M) during calcium ionophore s timulation did not change the PAF production. The synthesis of PAF was not influenced by the concentration of albumin in the incubation buff er. The PAF from stromal cells exhibited a hexadecyl chain at the sn-1 position of the molecule, as determined by reverse-phase HPLC. While stromal cells contained low amounts of PAF acetylhydrolase activity an d did not secrete it in the culture medium, they metabolized exogenous PAF with 1-alkyl-2-acyl-glycerophosphocholine and neutral lipids as t he major metabolic products. The present results are the first to demo nstrate the synthesis and metabolism of PAF by human bone marrow strom al cells. These data suggest that they might be a source of the PAF fo und in the human bone marrow and/or might be important in the regulati on of its levels. The role of PAF on the proliferation and functions o f human hematopoietic cells deserves investigation.