Involvement of tyrosine kinases in the activation of human peripheral blood neutrophils by granulocyte-macrophage colony-stimulating factor
Abstrak
The aim of the present study is to evaluate the involvement of human neutrophil tyrosine kinase(s) in the signal transduction mechanism of granulocyte-macrophage colony-stimulating factor (GM-CSF). Stimulation of neutrophils with GM-CSF resulted in a time- and dose-dependent phosphorylation of several proteins having estimated molecular weights of approximately 40, 55, 74, 97, 118, and 155 Kd, detected by immunoblot using a monoclonal antibody directed against phosphotyrosine. GM-CSF-induced tyrosine phosphorylation was inhibited in a dose- and time-dependent manner by the tyrosine kinase inhibitor erbstatin. Using this inhibitor, we were able to correlate tyrosine phosphorylation with several functional effects of GM-CSF on human neutrophils. Pretreatment of neutrophils with erbstatin before incubation with GM-CSF completely inhibited the GM-CSF-induced intracellular alkalinization, downregulation of the leukotriene B4 receptor, enhancement of fMet-Leu-Phe-induced intracellular calcium mobilization, as well as the accumulation of mRNA for the proto- oncogene c-fos. Taken together, these data suggest that tyrosine kinase activation in human neutrophils plays a critical regulatory role in both the stimulation and priming of neutrophil function by GM-CSF.
Penulis (5)
SR McColl
JF DiPersio
AC Caon
P Ho
PH Naccache
Akses Cepat
- Tahun Terbit
- 1991
- Bahasa
- en
- Total Sitasi
- 1×
- Sumber Database
- CrossRef
- DOI
- 10.1182/blood.v78.7.1842.bloodjournal7871842
- Akses
- Terbatas