Modulation of the production of leukemia associated inhibitor (LAI) and its interaction with granulocyte-macrophage colony-forming cells.
Leukemia associated inhibitor, LAI, reversibly inhibits DNA synthesis in normal human granulocyte-macrophage colony-forming units (CFU-GM). LAI is produced by myeloid leukemia cells, a subpopulation of normal nonadherent low-density mononuclear cells in peripheral blood and bone marrow, as well as by the human promyelocytic cell line HL-60. Normal low-density marrow cell absorbed LAI at 37 degrees C from HL-60 cell-conditioned medium. When normal marrow cells were treated with trypsin or chymotrypsin they lost their capacity to absorb LAI and also became insensitive to the inhibitory effect of LAI. These observations were taken as circumstantial evidence for the existence of a trypsin-sensitive LAI receptor on normal marrow cells, including CFU-GM. Glucocorticoid steroids (hydrocortisone, prednisolone, and dexamethasone) inhibited LAI production by acute myeloid leukemia (AML) cells, normal LAI-producing cells, and HL-60 cells. The fact that prostaglandin E1 (PGE) totally inhibited LAI production by normal cells and that indomethacin abrogated the inhibitory effect of adherent cells on LAI production suggested a role for adherent monocytic cells and PGE in the regulation of LAI production.
D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D004261:DNA Replication / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005293:Ferritins; D006098:Granulocytes / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D008264:Macrophages / Q000166:cytology*; D011239:Prednisolone / Q000494:pharmacology
D003115:Colony-Stimulating Factors; C020391:acidic isoferritin; D003907:Dexamethasone; D005293:Ferritins; D011239:Prednisolone; D006854:Hydrocortisone