ARACHIDONIC-ACID AND HUMAN BONE-MARROW STROMAL CELLS

Human bone marrow stromal cells regulate the growth of mal-row hematop oietic progenitors by secreting cytokines. Arachidonic acid (AA) is th e fatty acid precursor of prostaglandin E-2 (PGE(2)) and leukotriene B -4 (LTB4) that modulate the growth of human bone marrow progenitors. W e have investigated the incorporation of AA in human bone marrow strom al cell cultures, their production of PGE(2) and LTB4 and the effect o f AA on their growth. Gas chromatography analysis reveals the presence of AA in the human bone marrow plasma and in bone marrow stromal cell cultures. In stromal cells, [H-3]-AA is incorporated into triglycerid es and is later delivered into phospholipids. Prelabeling-chase experi ments indicate a preferential incorporation of AA into phosphatidyleth anolamine and no trafficking of labeled AA between phospholipid specie s. Bone marrow stromal cells release PGE(2) and LTB4 in response to ph orbol myristic acetate (PMA) (1 mu M) and tumor necrosis factor alpha (TNF-alpha) (10 ng/ml). Exogenous AA (up to 1 mu M) has no significant effect on cell growth. In conclusion, human bone marrow stromal cells capt exogenous AA and, thus, may participate to the control of marrow AA concentrations. They may also regulate human marrow hematopoiesis by secreting AA metabolites such as PGE(2) and LTB4. (C) 1998 Elsevier Science B.V.