Modulation of human marrow haematopoiesis by leucotrienes in vitro

The influence of products derived from the arachidonic acid 5-lipoxygenase (5-LO) pathway on normal human marrow haematopoiesis was studied using clonogenic assays. The leucotrienes (LT) B₄ and C₄ caused a reduction in granulocyte-macrophage (CFU-GM) as well as erythroid (CFU-E and BFU-E) colony numbers in a dose-dependent manner. Conversely, nordihydroguaiaretic acid (NDGA), a LT synthesis inhibitor, promoted proliferation of these colonies. The inhibitory effect of LTC₄ but not that of LTB₄ was abolished by FPL-55712, a LT antagonist; the enhanced colony growth induced by NDGA was reversed by both LTB₄ and LTC₄. LTD₄ had no significant effect on colony growth despite its structural similarity to LTC₄, which implies that the haematopoietic suppression by LTB₄ and LTC₄ is specific for these compounds. Depletion of marrow T-cells or removal of adherent cells, or both, did not alter the response to LTB₄ and LTC₄, suggesting that LT action is exerted directly on progenitor cells and probably is not mediated by other cell populations. Our studies show that the 5-LO pathway is functional in these culture systems and yields products with inhibitory properties. The 5-LO pathway may have an important regulatory function in normal marrow haematopoiesis.