Molecular mechanisms involved in macrophage survival, proliferation, activation or apoptosis.
Macrophages play a critical role during the immune response. Like other cells of the immune system, macrophages are produced in large amounts and most of them die through apoptosis. Macrophages survive in the presence of soluble factors, such as IFN-gamma, or extracellular matrix proteins like decorin. The mechanism toward survival requires the blocking of proliferation at the G1/S boundary of the cell cycle that is mediated by the cyclin-dependent kinase (cdk) inhibitor, p27kip and the induction of a cdk inhibitor, p21waf1. At the inflammatory loci, macrophages need to proliferate or become activated in order to perform their specialized activities. Although the stimuli inducing proliferation and activation follow different intracellular pathways, both require the activation of extracellular signal-regulated kinases (ERKs) 1 and 2. However, the kinetics of ERK-1/2 activation is different and is determined by the induction of the MAP-kinase phosphatase-1 (MKP-1) that dephosphorilates ERK-1/2. This phosphatase plays a critical role in the process of proliferation versus activation of the macrophages.
Xaus
J
J
Departament de Fisiologia (Biologia del Macròfag), Facultat de Biologia and Fundació August Pi i Sunyer, Universitat de Barcelona, Spain.
Comalada
M
M
Valledor
A F
AF
Cardó
M
M
Herrero
C
C
Soler
C
C
Lloberas
J
J
Celada
A
A
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018797:Cell Cycle Proteins; D002455:Cell Division; D002470:Cell Survival; D054638:Dual Specificity Phosphatase 1; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases