Expression of mRNA 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 human granulocytes and bone marrow cells was examined using ribonuclease protection 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), but not neurotrophin-3 (NT-3). Moreover, the inflammatory mediator leukotriene B4 (LTB4) up-regulated the expression of NT-4 mRNA in granulocytes, but did not affect the expression of other neurotrophin mRNAs. Granulocytes generally lacked expression of mRNA coding for neurotrophin receptors. In contrast, human bone marrow cells consistently expressed 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 bone marrow cells generally expressed only low levels of mRNA encoding BDNF and NT-4. Expression of mRNA encoding NGF and NT-3 was not detected. However, significantly increased expression of BDNF mRNA was observed when bone marrow cells from patients with chronic myeloproliferative disorders (MPD) were analyzed. The results suggest that neurotrophins may act as granulocyte-derived effector molecules and that human bone marrow cells may be targets for these compounds, in particular BDNF and NT-4.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
M A
MA
Laurenzi
T
T
Beccari
L
L
Stenke
M
M
Sjölinder
S
S
Stinchi
J A
JA
Lindgren
D001854:Bone Marrow Cells / Q000737:chemistry* / Q000276:immunology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000276:immunology; D002908:Chronic Disease; D015870:Gene Expression / Q000276:immunology; D006098:Granulocytes / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007975:Leukotriene B4 / Q000276:immunology / Q000494:pharmacology*; D009196:Myeloproliferative Disorders / Q000276:immunology*; D009414:Nerve Growth Factors / Q000235:genetics* / Q000276:immunology; D018696:Neuroprotective Agents / Q000276:immunology; D020933:Neurotrophin 3; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D007975:Leukotriene B4; D020794:Receptor Protein-Tyrosine Kinases; C073922:neurotrophin 4