Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival

Witko‐Sarsat, Véronique; Mocek, Julie; Bouayad, Dikra; Tamassia, Nicola; Ribeil, Jean-Antoine; Candalh, Céline; Davezac, Noélie; Reuter, Nathalie; Mouthon, Luc; Hermine, Olivier; Pederzoli-Ribeil, Magali; Cassatella, Marco A.

doi:10.1084/jem.20092241

Cited by 141 publications

(192 citation statements)

References 48 publications

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…Exposure of neutrophils to TNF-related apoptosis-inducing ligand (TRAIL) resulted in enhanced apoptosis (Fig. 6F), consistent with previous studies showing the importance of extrinsic induced apoptotic pathways in neutrophil death (27,31,41). Inclusion of PAI-1 in the neutrophil cultures diminished the proapoptotic effects of TRAIL (Fig.…”

Section: Pai-1-dependent Activation Of Phosphatidylinositol 3-kinase supporting

confidence: 90%

Inhibition of neutrophil apoptosis by PAI-1

Żmijewski¹,

Bae

Deshane

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Increased circulating and tissue levels of plasminogen activator inhibitor 1 (PAI-1) are often present in severe inflammatory states associated with neutrophil activation and accumulation and correlate with poor clinical outcome from many of these conditions. The mechanisms by which PAI-1 contributes to inflammation have not been fully delineated. In the present experiments, we found that addition of PAI-1 to neutrophil cultures diminished the rate of spontaneous and TNF-related apoptosis-inducing ligand-induced apoptotic cell death. The effects of PAI-1 on cell viability were associated with activation of antiapoptotic signaling pathways, including upregulation of PKB/Akt, Mcl-1, and Bcl-xL. Although urokinase-plasminogen activator receptor, lipoprotein receptor-related protein, and vitronectin are primary ligands for PAI-1, these molecules were not involved in mediating its antiapoptotic properties. In contrast, blocking pertussis toxin-sensitive G protein-coupled receptors and selective inhibition of phosphatidylinositide 3-kinase reversed the ability of PAI-1 to extend neutrophil viability. The antiapoptotic effects of PAI-1 were also evident under in vivo conditions during LPS-induced acute lung injury, where enhanced apoptosis was present among neutrophils accumulating in the lungs of PAI-1−/−compared with PAI-1+/+mice. These results demonstrate a novel antiapoptotic role for PAI-1 that may contribute to its participation in neutrophil-associated inflammatory responses.

show abstract

Section: Pai-1-dependent Activation Of Phosphatidylinositol 3-kinase supporting

confidence: 90%

Inhibition of neutrophil apoptosis by PAI-1

Żmijewski¹,

Bae

Deshane

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Proliferating cell nuclear antigen (PCNA) has been identical to cyclin and it is a nuclear factor involved in DNA replication and repair of proliferating cells. PCNA can associate with several procaspases to block their activation for presenting anti-apoptotic activities [73,74]. These reports and the present results altogether suggest that MCs may induce apoptosis and inflammatory in the brain [12,13].…”

Section: Discussionsupporting

confidence: 72%

A proteomic analysis of prenatal transfer of microcystin-LR induced neurotoxicity in rat offspring

Zhao

Chen

2015

Journal of Proteomics

View full text Add to dashboard Cite

“…Nonetheless, some results suggest that the regulation of constitutive apoptosis in neutrophils from patients with chronic inflammatory diseases such as rheumatoid arthritis may be disturbed, and that they have a lower rate of apoptosis (46). Along the same lines, we have recently reported high levels of the cytoplasmic proliferating cell nuclear Ag, thus reflecting a prosurvival state in neutrophils from GPA patients (47). Although in this study no difference was observed in PS externalization in patients with ANCA-associated vasculitis, it has been recently reported that neutrophils from these patients had a delayed apoptosis (48).…”

Section: Role Of Macrophages In the Modulation Of Autoimmunity In Gpamentioning

confidence: 77%

Proteinase 3, the Autoantigen in Granulomatosis with Polyangiitis, Associates with Calreticulin on Apoptotic Neutrophils, Impairs Macrophage Phagocytosis, and Promotes Inflammation

Gabillet

Millet

Pederzoli-Ribeil

et al. 2012

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Proteinase 3 (PR3) is the target of anti-neutrophil cytoplasm Abs in granulomatosis with polyangiitis, a form of systemic vasculitis. Upon neutrophil apoptosis, PR3 is coexternalized with phosphatidylserine and impaired macrophage phagocytosis. Calreticulin (CRT), a protein involved in apoptotic cell recognition, was found to be a new PR3 partner coexpressed with PR3 on the neutrophil plasma membrane during apoptosis, but not after degranulation. The association between PR3 and CRT was demonstrated in neutrophils by confocal microscopy and coimmunoprecipitation. Evidence for a direct interaction between PR3 and the globular domain of CRT, but not with its P domain, was provided by surface plasmon resonance spectroscopy. Phagocytosis of apoptotic neutrophils from healthy donors was decreased after blocking lipoprotein receptor-related protein (LRP), a CRT receptor on macrophages. In contrast, neutrophils from patients with granulomatosis with polyangiitis expressing high membrane PR3 levels showed a lower rate of phagocytosis than those from healthy controls not affected by anti-LRP, suggesting that the LRP-CRT pathway was disturbed by PR3-CRT association. Moreover, phagocytosis of apoptotic PR3-expressing cells potentiated proinflammatory cytokine in vitro by human monocyte-derived macrophages and in vivo by resident murine peritoneal macrophages, and diverted the anti-inflammatory response triggered by the phagocytosis of apoptotic cells after LPS challenge in thioglycolate-elicited murine macrophages. Therefore, membrane PR3 expressed on apoptotic neutrophils might amplify inflammation and promote autoimmunity by affecting the anti-inflammatory “reprogramming” of macrophages.

show abstract

Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival

Abstract: Cytosolic proliferating cell nuclear antigen (PCNA) binds to procaspases and protects human neutrophils from apoptosis.

Cited by 141 publications

References 48 publications

Inhibition of neutrophil apoptosis by PAI-1

Inhibition of neutrophil apoptosis by PAI-1

A proteomic analysis of prenatal transfer of microcystin-LR induced neurotoxicity in rat offspring

Proteinase 3, the Autoantigen in Granulomatosis with Polyangiitis, Associates with Calreticulin on Apoptotic Neutrophils, Impairs Macrophage Phagocytosis, and Promotes Inflammation

Contact Info

Product

Resources

About