Back to Search
Start Over
Age-related impairment of GM-CSF-induced signalling in neutrophils: role of SHP-1 and SOCS proteins
- Source :
- Ageing research reviews. 6(2)
- Publication Year :
- 2006
-
Abstract
- Functional activities of mature human neutrophils are strongly influenced by the pro-inflammatory cytokine granulocyte macrophage-colony stimulating factor (GM-CSF). Accordingly, a defective response to GM-CSF might have dramatic consequences for neutrophil functions and the host defence against infections. Such an event is most likely to occur in senescence. A number of studies have, in fact, reported an impairment of the GM-CSF capacity to prime and/or to activate respiratory burst, as well as to delay apoptotic events, in neutrophils from elderly individuals. In the last 2 decades many efforts have been made to explore at molecular levels the mechanism underlying these defects. Recent studies let us depict a scenario in which an increased activity of inhibitory molecules, such as Src homology domain-containing protein tyrosine phosphatase-1 (SHP-1) and suppressors of cytokine signalling (SOCS), is responsible for the age-related failure of GM-CSF to stimulate neutrophil functions via inhibition of Lyn-, phosphoinositide 3-kinase (PI3-K)/extracellular signal-regulated kinase (ERK)- and signal transducers and activators of transcription (STAT)-dependent pathways. The control of SHP-1 and/or SOCS activity might therefore be an important therapeutic target for the restoration of normal immune responses during senescence.
- Subjects :
- MAPK/ERK pathway
Aging
Neutrophils
medicine.medical_treatment
Suppressor of Cytokine Signaling Proteins
Protein tyrosine phosphatase
Biology
Biochemistry
Suppressor of cytokine signalling
Membrane Microdomains
LYN
Protein Phosphatase 1
medicine
Humans
Molecular Biology
Kinase
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Granulocyte-Macrophage Colony-Stimulating Factor
Cell biology
Respiratory burst
Up-Regulation
Cytokine
Neurology
Immunology
Biotechnology
Proto-oncogene tyrosine-protein kinase Src
Signal Transduction
Subjects
Details
- ISSN :
- 15681637
- Volume :
- 6
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Ageing research reviews
- Accession number :
- edsair.doi.dedup.....829b9583ad1f8880d1926f8da72617ca