EXPRESSION OF MESSENGER-RNA ENCODING NEUROTROPHINS AND NEUROTROPHIN RECEPTORS IN HUMAN GRANULOCYTES AND BONE-MARROW CELLS - ENHANCED NEUROTROPHIN-4 EXPRESSION INDUCED BY LTB4

The expression of neurotrophin and neurotrophin receptor mRNAs in huma n granulocytes and bone marrow cells was examined using ribonuclease p rotection assay and reverse transcription -polymerase chain reaction. The granulocytes expressed mRNA coding for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-4 (NT-4), b ut trot neurotrophin-3 (NT-3), Moreover, the inflammatory mediator leu kotriene B-4 (LTB4) up-regulated the expression of NT-4 mRNA in granul ocytes, but did not affect the expression of other neurotrophin mRNAs. Granulocytes generally lacked expression of mRNA coding for neurotrop hin receptors. In contrast, human bone marrow cells consistently expre ssed mRNA for trkB (the BDNF and NT-4 receptor) and displayed variable expression of mRNA coding for trkA (the tyrosine kinase NGF receptor) and LNGFR (the low-affinity NGF receptor), whereas mRNA for trkC (the NT-3 receptor) was not expressed. Contrary to granulocytes, normal bo ne marrow cells generally expressed only low levels of mRNA encoding B DNF and NT-4. Expression of mRNA encoding NGF and NT-3 was not detecte d. However, significantly increased expression of BDNF mRNA was observ ed when bone marrow cells from patients with chronic myeloproliferativ e disorders (MPD) were analyzed. The results suggest that neurotrophin s may act as granulocyte-derived effector molecules and that human bon e marrow cells may be targets for these compounds, in particular BDNF and NT-4.