Molecular Mechanisms Involved in Macrophage Survival, Proliferation, Activation or Apoptosis

Xaus, Jordi; Comalada, Mònica; Valledor, Annabel F.; Cardó, Marina; Herrero, Carmen; Soler, Concepció; Lloberas, Jorge; Celada, Antonio

doi:10.1078/0171-2985-00091

Cited by 111 publications

(95 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another possible reason for increased glomerular retention of transferred cells is inhibition of macrophage apoptosis. We have previously identified apoptosis of glomerular macrophages in rat anti-GBM disease, suggesting that this is an important mechanism for the removal of macrophages from the inflamed glomerulus (28), and IFN-␥ has been shown to inhibit macrophage apoptosis (29). The second mechanism to account for IFN-␥ augmentation of renal injury is that IFN-␥ activation caused a significantly greater degree of renal injury (proteinuria and mesangial cell proliferation) per transferred glomerular macrophage compared with unstimulated macrophages.…”

Section: Discussionmentioning

confidence: 99%

Interferon-γ Augments Acute Macrophage-Mediated Renal Injury Via a Glucocorticoid-Sensitive Mechanism

Ikezumi¹,

Atkins²,

Nikolic-Paterson³

2003

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. Macrophages have been implicated in causing renal injury in both human and experimental kidney disease. The aim of the current study was to determine whether modulating the state of macrophage activation directly affects the capacity of these cells to cause renal injury. This was investigated using an adoptive transfer model in which macrophage activation can be manipulated in vitro, using interferon-␥ (IFN-␥) or dexamethasone (Dex), and then macrophage-mediated renal injury determined in vivo. In this model, rats were made leukopenic by administration of cyclophosphamide (CyPh). Two days later (day 0), animals were injected with sheep anti-GBM serum followed by a single injection of rat NR8383 macrophages on day 1 and then killed 3 or 24 h after cell transfer. NR8383 macrophages were incubated IFN-␥ and/or Dex before adoptive transfer into animals. Induction of proteinuria and glomerular cell proliferation (PCNAϩ cells) in this model was dependent on transfer of NR8383 macrophages. Exposure of macrophages to IFN-␥ for 18 h (but not 3 h) before transfer caused a twofold increase in the degree of proteinuria and glomerular cell proliferation compared with unstimulated cells

show abstract

Section: Discussionmentioning

confidence: 99%

Interferon-γ Augments Acute Macrophage-Mediated Renal Injury Via a Glucocorticoid-Sensitive Mechanism

Ikezumi¹,

Atkins²,

Nikolic-Paterson³

2003

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…However, it is noteworthy that inhibition of Erk1/2 activation did reduce the number of hematopoietic progenitors as measured by the CFC assay. This effect may be explained by the fact that most cells remaining after 14 days in culture in the absence of exogenous cytokines are differentiated, and studies have shown that the cytokine-induced survival of differentiated cells, such as macrophages, is mediated mainly by the PI 3-kinase pathway and not the Erk1/2 MAP kinase pathway (49,50). Thus, this may indicate that hematopoietic progenitors are more dependent on the Erk1/2 MAP kinase pathway for VEGFR-2-induced survival than more mature cells.…”

Section: Vegfr-2 Signaling In Hematopoietic Progenitorsmentioning

confidence: 99%

Vascular Endothelial Growth Factor Receptor-2 Induces Survival of Hematopoietic Progenitor Cells

Larrivée

Lane

Pollet

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Vascular endothelial growth factor (VEGF) and its receptors play an essential role in the formation and maintenance of the hematopoietic and vascular compartments. The VEGF receptor-2 (VEGFR-2) is expressed on a population of hematopoietic cells, although its role in hematopoiesis is still unclear. In this report, we have utilized a strategy to selectively activate VEGFR-2 and study its effects in primary bone marrow cells. We found that VEGFR-2 can maintain the hematopoietic progenitor population in mouse bone marrow cultured in the absence of exogenous cytokines. Maintenance of the hematopoietic progenitor population is due to increased cell survival with minimal effect on proliferation. Progenitor survival is mainly mediated by activation of the phosphatidylinositol 3 -kinase/Akt pathway. Although VEGFR-2 also activated Erk1/2 mitogen-activated protein kinase, it did not induce cell proliferation, and blockade of this pathway only partially decreased VEGFR-2-mediated survival of hematopoietic progenitors. Thus, the role of VEGFR-2 in hematopoiesis is likely to maintain survival of hematopoietic progenitors through the activation of antiapoptotic pathways.

show abstract

Section: Introductionmentioning

confidence: 99%

“…In response to needs, tissue macrophages proliferate, further differentiate to more specialized macrophagic populations, or become activated. Macrophages, like many other cells of the immune system, are produced in large excess and most undergo apoptosis [2].In the presence of M-CSF, macrophages differentiate and proliferate. However, the proliferation of these cells is blocked when they are activated by Gram-negative LPS or by .…”

mentioning

confidence: 99%

CREB and AP‐1 activation regulates MKP‐1 induction by LPS or M‐CSF and their kinetics correlate with macrophage activation versus proliferation

et al. 2009

View full text Add to dashboard Cite

MAPK phosphatase-1 (MKP-1) is a protein phosphatase that plays a crucial role in innate immunity. This phosphatase inactivates ERK1/2, which are involved in two opposite functional activities of the macrophage, namely proliferation and activation. Here we found that although macrophage proliferation and activation induce MKP-1 with different kinetics, gene expression is mediated by the proximal promoter sequences localized between À380 and À180 bp. Mutagenesis experiments of the proximal element determined that CRE/AP-1 is required for LPS-or M-CSF-induced activation of the MKP-1 gene. Moreover, the results from gel shift analysis and chromatin immunoprecipitation indicated that c-Jun and CREB bind to the CRE/AP-1 box. The distinct kinetics shown by M-CSF and LPS correlates with the induction of JNK and c-jun, as well as the requirement for Raf-1. The signal transduction pathways that activate the induction of MKP-1 correlate kinetically with induction by M-CSF and LPS.Key words: Activation . Kinases . Macrophage . Phosphatases . Proliferation IntroductionMacrophages perform critical functions during the immune response. These cells are regulators of homeostasis and play an important role in innate and acquired immunity during infection, tumor growth, and wound healing [1]. In response to needs, tissue macrophages proliferate, further differentiate to more specialized macrophagic populations, or become activated. Macrophages, like many other cells of the immune system, are produced in large excess and most undergo apoptosis [2].In the presence of M-CSF, macrophages differentiate and proliferate. However, the proliferation of these cells is blocked when they are activated by Gram-negative LPS or by . Activation causes many biochemical, morphological and functional modifications. Macrophage response to M-CSF and LPS involves the phosphorylation of the three members of the MAPK family [4].MAPK are critical components of signal transduction pathways activated by a range of stimuli and they mediate a number of physiological and pathological changes in cell function [5,6]. MAPK activation requires phosphorylation on a threonine and tyrosine residue located in the activation loop. This process is reversible even in the continued presence of activating stimuli, thereby indicating that protein phosphatases regulate MAPK [7]. Although MAPK are conserved evolutionary pathways present in eukaryotic cells, the kinetics of activation and their subcellular compartmentalization are cell type-specific, and they orchestrate differential cellular responses. For example, in neuronal cells, sustained MAPK phosphorylation of even days is required for cellular activation or differentiation, while in fibroblasts, phosphorylation of this kinase family is very short. In contrast, to Immunol. 2009. 39: 1902-1913 Cristina Casals-Casas et al. 1902 achieve proliferation, extended activation of MAPK is required in these cells [6,7]. The correct spatio-temporal regulation of MAPK signalling is crucial in determining cellular responses to g...

show abstract

Molecular Mechanisms Involved in Macrophage Survival, Proliferation, Activation or Apoptosis

Cited by 111 publications

References 35 publications

Interferon-γ Augments Acute Macrophage-Mediated Renal Injury Via a Glucocorticoid-Sensitive Mechanism

Interferon-γ Augments Acute Macrophage-Mediated Renal Injury Via a Glucocorticoid-Sensitive Mechanism

Vascular Endothelial Growth Factor Receptor-2 Induces Survival of Hematopoietic Progenitor Cells

CREB and AP‐1 activation regulates MKP‐1 induction by LPS or M‐CSF and their kinetics correlate with macrophage activation versus proliferation

Contact Info

Product

Resources

About