Monocytes of allergics and non-allergics produce, store and release the neurotrophins NGF, BDNF and NT-3.
BACKGROUND
Recent studies have shown that neurotrophins (NTs) are involved in inflammatory processes. Elevated plasma levels of NTs were found allergic diseases with the highest levels in allergic asthma. However, the exact cellular sources involved in the regulation and release of neurotrophins in allergic inflammation are still not well defined.


OBJECTIVE
The aim of this study was to assess whether monocytes of allergic and non-allergic subjects produce, store and release the neurotrophins NGF, BDNF and NT-3.


METHODS
Monocytes of allergic and non-allergic donors were purified by immunomagnetic selection. APAAP-staining for the presence of NTs and their receptors was performed. RT-PCR and Western blot evaluated the production and storage of NTs. Monocytes were incubated and supernatants were collected for measurement of neurotrophic factors after stimulation with lipopolysaccharide (LPS) as inflammatory stimulus. The neurotrophin content in lysates and cell culture supernatants was determined by ELISA.


RESULTS
Human monocytes express the neurotrophins NGF, BDNF and NT-3 but also their specific receptors TrkA, TrkB and TrkC. RT-PCR amplification of isolated mRNA demonstrated expression of the examined neurotrophins. Proteins were detectable by Western blot. NTs were found in the monocyte lysates and supernatants at different levels in allergic and non-allergic donors. Cell stimulation with LPS leads to release of NGF and NT3.


CONCLUSIONS
Monocytes, produce, store and release NGF, BDNF and NT-3. They are a possible source of elevated neurotrophin levels found in allergy and asthma.
Rost
Bettina
B
Allergy and Asthma Clinic, Department of medicine Infectious and Respiratory diseases, Charité, Humboldt University, Augustenburger Platz 1, Berlin 13353, Germany.
Hanf
Gerald
G
Ohnemus
Ulrich
U
Otto-Knapp
Ralf
R
Groneberg
David A
DA
Kunkel
Gert
G
Noga
Oliver
O
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003470:Culture Media; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019208:Brain-Derived Neurotrophic Factor; D003470:Culture Media; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases