The histamine H4 receptor regulates the inflammatory response. However, it is not known whether this receptor has a functional role in human neutrophils. We found that fMLP (1 μM), but not histamine (0.1-1 μM), induced Mac-1-dependent adhesion, polarization, and degranulation (release of lactoferrin). A pretreatment of neutrophils with histamine (0.001-1 μM) or JNJ 28610244 (0.1-10 μM), a specific H4 receptor agonist, led to inhibition of degranulation. Total inhibition of degranulation was obtained with 0.1 μM histamine and 10 μM JNJ 28610244. Furthermore, such inhibition by histamine of degranulation was reversed by JNJ 7777120 and JNJ 28307474, two selective H4 receptor antagonists. However, neither histamine nor the H4 receptor agonist JNJ 28610244 prevented fMLP-induced, Mac-1-dependent adhesion, indicating that the H4 receptor may block signals emanating from Mac-1-controlling degranulation. Likewise, engagement of the H4 receptor by the selective agonist JNJ 28610244 blocked Mac-1-dependent activation of p38 MAPK, the kinase that controls neutrophil degranulation. We also show expression of the H4 receptor at the mRNA level in ultrapure human neutrophils and myeloid leukemia PLB-985 cells. We concluded that engagement of this receptor by selective H4 receptor agonists may represent a good, therapeutic approach to accelerate resolution of inflammation.
- MeSH
- akutní promyelocytární leukemie patologie MeSH
- antigen-1 spojený s lymfocytární funkcí chemie MeSH
- buněčná adheze účinky léků fyziologie MeSH
- cytochalasin B farmakologie MeSH
- degranulace buněk * účinky léků MeSH
- fibrinogen MeSH
- histamin farmakologie MeSH
- indoly farmakologie MeSH
- konformace proteinů účinky léků MeSH
- kultivované buňky MeSH
- lidé MeSH
- makrofágový antigen 1 fyziologie MeSH
- MAP kinasový signální systém účinky léků MeSH
- messenger RNA biosyntéza genetika MeSH
- mitogenem aktivované proteinkinasy p38 fyziologie MeSH
- N-formylmethionin-leucyl-fenylalanin farmakologie MeSH
- nádorové buněčné linie MeSH
- neutrofily účinky léků fyziologie MeSH
- oximy farmakologie MeSH
- piperaziny farmakologie MeSH
- piperidiny farmakologie MeSH
- pyridiny farmakologie MeSH
- receptory histaminu fyziologie MeSH
- receptory spřažené s G-proteiny agonisté antagonisté a inhibitory fyziologie MeSH
- tvar buňky účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
