Identification of highly elevated levels of melatonin in bone marrow: its origin and significance

Bone marrow is an important tissue in generation of immunocompetent and per ipheral blood cells. The progenitors of hematopoietic cells in bone marrow exhibit continuous proliferation and differentiation and they are highly vu lnerable to acute or chronic oxidative stress. In this investigation, highl y elevated levels of the antioxidant melatonin were identified in rat bone marrow using immunocytochemistry, radioimmunoassay, high performance liquid chromatography with electrochemical detection and mass spectrometry. Night -time melatonin concentrations (expressed as pg melatonin/mg protein) in th e bone marrow of rats were roughly two orders of magnitude higher than thos e in peripheral blood. Measurement of the activities of the two enzymes (N- acetyltransferase (NAT) and hydroxyindole-O-methoxyltransferase (HIOMT)) wh ich synthesize melatonin from serotonin showed that bone marrow cells have measurable NAT activity, but they have very low levels of HIOMT activity (a t the one time they were measured), From these studies we could not definit ively determine whether melatonin was produced in bone marrow cells or else where. To investigate the potential pineal origin of bone marrow melatonin, long-term (8-month) pinealectomized rats were used to ascertain if the pin eal gland is the primary source of this antioxidant. The bone marrow of pin ealectomized rats, however, still exhibited high levels of melatonin. These results indicate that a major portion of the bone marrow's melatonin is of extrapineal origin. Immunocytochemistry clearly showed a positive melatoni n reaction intracellularly in bone marrow cells. A melatonin concentrating mechanism in these cells is suggested by these findings and this may involv e a specific melatonin binding protein. Since melatonin is an endogenous fr ee radical scavenger and an immune-enhancing agent, the high levels of mela tonin in bone marrow cells may provide on-site protection to reduce oxidati ve damage to these highly vulnerable hematopoietic cells and may enhance th e immune capacity of cells such as lymphocytes. (C) 1999 Published by Elsev ier Science B.V. All rights reserved.