Expression and function of the endothelial protein C receptor in human neutrophils

Sturn, Daniel H.; Kaneider, Nicole C.; Feistritzer, Clemens; Djanani, Angela; Fukudome, Kenji; Wiedermann, Christian J.

doi:10.1182/blood-2002-12-3880

Cited by 178 publications

(168 citation statements)

References 42 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…Our results are consistent with subgroup analysis of the PROWESS trial, which revealed that improvement in survival associated with recombinant activated protein C therapy was similar for patients with Gram-positive and Gram-negative bacterial sepsis (46). Our results are also consistent with studies by Sturn et al (34) that examined the effect of activated protein C on neutrophil phagocytosis. The authors reported that activated protein C inhibited neutrophil chemotaxis but did not affect neutrophil respiratory bursts nor phagocytic activity.…”

Section: Discussionsupporting

confidence: 82%

“…To date, the only known cellular receptor for activated protein C is the EPCR, a 46-kDa singlechain transmembrane glycoprotein homologous to the MHC class I/CD1 family of molecules (33). EPCR was identified originally on vascular endothelial cells and has since been detected in neutrophils (34), monocytes (34), and in the monocytic cell line THP-1 (35). Recent studies in endothelial cells suggest that the antiapoptotic effect of activated protein C is mediated by EPCR and PAR-1 and EPCR (19 -21).…”

Section: Requirement Of Epcr and Par-1 For The Antiapoptotic Effect Omentioning

confidence: 99%

See 1 more Smart Citation

Modulation of Monocyte Function by Activated Protein C, a Natural Anticoagulant

Stephenson¹,

Toltl²,

Beaudin

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

Activated protein C is the first effective biological therapy for the treatment of severe sepsis. Although activated protein C is well established as a physiological anticoagulant, emerging data suggest that it also exerts anti-inflammatory and antiapoptotic effects. In this study, we investigated the ability of activated protein C to modulate monocyte apoptosis, inflammation, phagocytosis, and adhesion. Using the immortalized human monocytic cell line THP-1, we demonstrated that activated protein C inhibited camptothecin-induced apoptosis in a dose-dependent manner. The antiapoptotic effect of activated protein C requires its serine protease domain and is dependent on the endothelial cell protein C receptor and protease-activated receptor-1. In primary blood monocytes from healthy individuals, activated protein C inhibited spontaneous apoptosis. With respect to inflammation, activated protein C inhibited the production of TNF, IL-1β, IL-6, and IL-8 by LPS-stimulated THP-1 cells. Activated protein C did not influence the phagocytic internalization of Gram-negative and Gram-positive bioparticles by THP-1 cells or by primary blood monocytes. Activated protein C also did not affect the expression of adhesion molecules by LPS-stimulated blood monocytes nor the ability of monocytes to adhere to LPS-stimulated endothelial cells. We hypothesize that the protective effect of activated protein C in sepsis reflects, in part, its ability to prolong monocyte survival in a manner that selectively inhibits inflammatory cytokine production while maintaining phagocytosis and adherence capabilities, thereby promoting antimicrobial properties while limiting tissue damage.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Requirement Of Epcr and Par-1 For The Antiapoptotic Effect Omentioning

confidence: 99%

Modulation of Monocyte Function by Activated Protein C, a Natural Anticoagulant

Stephenson¹,

Toltl²,

Beaudin

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…For example, THBD and EPCR are both expressed in keratinocytes where their anti-inflammatory roles are particularly relevant to the wound-healing process [35][36][37]. The anti-inflammatory properties of EPCR have also been demonstrated in lung pneumocytes [38], intestinal dendritic cells [39], and in neutrophils [40]. Our findings, as far as we are aware, are the first report of the existence of THBD and EPCR in the anterior pituitary gland.…”

Section: Discussionmentioning

confidence: 51%

Adenosine regulates thrombomodulin and endothelial protein C receptor expression in folliculostellate cells of the pituitary gland

Rees

Giles

Lewis

et al. 2009

Purinergic Signalling

View full text Add to dashboard Cite

Adenosine stimulates the release of interleukin 6 (IL-6) and vascular endothelial growth factor from folliculostellate cells of the anterior pituitary gland indicating that such cells are also involved in the communication between the immune and endocrine systems during stress and inflammation. In order to understand the precise actions of adenosine on folliculostellate cells, DNA microarray analysis was used to determine global changes in gene expression. Hierarchical clusters revealed, of the genes that had altered expression, the majority were suppressed and many, such as B cell translocation gene 2 and cyclindependent kinase inhibitor 2b were related to cell cycle arrest or inhibition of proliferation. Several of the upregulated genes were associated with cytokine signalling or membrane receptor activity. The most notable of these being IL-6, sulfiredoxin 1, endothelial protein C receptor (EPCR) and thrombomodulin (THBD) which can all play a role in controlling inflammation. The EPCR and THBD pathway is well known in anti-coagulation but also has anti-inflammatory and anti-apoptotic properties. Upregulation of EPCR and THBD in folliculostellate cells was confirmed by qRT-PCR and western blotting analysis and their expression were also demonstrated in many of the hormone-secreting cells of the anterior pituitary gland. Our findings suggest that adenosine can stimulate expression of stress and inflammation related genes from folliculostellate cells of the anterior pituitary gland. These genes include EPCR and THBD, neither of which has been previously identified in the pituitary gland.

show abstract

“…Natural anti-coagulants do not only oppose the coagulation cascade. Firstly, anti-coagulant processes diminish leukocyte chemotaxis [ 159 ]. They suppress endothelial-cell interactions [ 160 ] as well as apoptosis [ 161 , 162 ].…”

Section: Anti-coagulantsmentioning

confidence: 99%

“…The effect of different concentrations of TF on coagulation kinetics (initiation, propagation and final clot strength) in human plasma is determined [ 159 ]. These analyses demonstrated that an ionised calcium concentration between 1 and 2 mM in the presence of 2000 pM TF was optimal with regard to plateau of time of onset of clotting, velocity of clot formation and maintenance of final clot strength [ 159 ]. Thus, this concentration of TF was utilised in subsequently presented scanning electron microscopy (SEM) data and viscoelastic analysis.…”

Section: Fibrin and Platelet Analysismentioning

confidence: 99%