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.