Plasmin Promotes an Endothelium-Dependent Adhesion of Neutrophils

Montrucchio, Giorgia; Lupia, Enrico; Martino, Antonella De; Silvestro, L; Savu, Simona Rizea; Cacace, Gianluigi; Filippi, P; Emanuelli, G; Camussi, Giovanni

doi:10.1161/01.cir.93.12.2152

Cited by 53 publications

(20 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thereby, cell-associated plasmin might promote cellular migration (10). Indeed, plasmin-induced neutrophil aggregation and adhesion in vitro (46,47). Moreover, studies using Plg Ϫ/Ϫ mice have provided in vivo evidence for an essential role of the plasminogen system in thioglycolate-induced macrophage migration (21).…”

Section: Discussionmentioning

confidence: 99%

Endogenous Tissue-Type Plasminogen Activator Is Protective duringEscherichia coli-Induced Abdominal Sepsis in Mice

Renckens

Roelofs

Florquin

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

Sepsis is associated with enhanced production of tissue-type plasminogen activator (tPA). We investigated the function of endogenous tPA in the immune responses to Escherichia coli-induced abdominal sepsis using tPA gene-deficient (tPA−/−) and normal wild-type (WT) mice. tPA−/− mice demonstrated an impaired defense against E. coli peritonitis as indicated by higher bacterial loads at the primary site of the infection, enhanced dissemination, and reduced survival. The protective function of tPA was independent of plasmin since plasminogen gene-deficient (Plg−/−) mice were indistinguishable from WT mice. Relative to WT mice, tPA−/− mice demonstrated similar neutrophil counts in the peritoneal cavity despite much higher bacterial loads and higher local concentrations of neutrophil attracting chemokines, suggesting a reduced migratory response. In line, tPA−/− mice demonstrated a reduced thioglycolate-induced neutrophil influx into the peritoneal cavity and i.p. injection of WT mice with a replication-defective adenoviral vector expressing tPA caused an enhanced cell migration to the peritoneal cavity during E. coli peritonitis. These findings identify a novel protective function of tPA in abdominal sepsis caused by E. coli that seems independent of its role in the generation of plasmin.

show abstract

Section: Discussionmentioning

confidence: 99%

Endogenous Tissue-Type Plasminogen Activator Is Protective duringEscherichia coli-Induced Abdominal Sepsis in Mice

Renckens

Roelofs

Florquin

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Bound NAPlr then traps plasmin and maintains its activity, which may induce glomerular damage in situ by degrading the GBM by itself or by activating pro-MMP. Plasmin activity may also mediate inflammation by activating and accumulating monocytes and neutrophils in situ (36,37). Such glomerular damage may induce urine abnormalities during the latent period of the disease.…”

Section: Discussionmentioning

confidence: 99%

Glomerular Plasmin-Like Activity in Relation to Nephritis-Associated Plasmin Receptor in Acute Poststreptococcal Glomerulonephritis

Oda

Yamakami

Omasu³

et al. 2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

A nephritogenic antigen for acute poststreptococcal glomerulonephritis (APSGN) was isolated recently from group A streptococcus and termed nephritis-associated plasmin receptor (NAPlr). In vitro experimental data indicate that the pathogenic role of NAPlr occurs through its ability to bind to plasmin and maintain its proteolytic activity. However, the mechanism whereby this antigen induces glomerular damage in vivo has not been fully elucidated. Renal biopsy tissues from 17 patients with APSGN, 8 patients with rapidly progressive glomerulonephritis, and 10 normal kidneys were analyzed in this study. Plasmin-like activity was assessed on cryostat sections by in situ zymography with a plasmin-sensitive synthetic substrate. Serial sections were simultaneously assessed for NAPlr deposition by immunofluorescence staining. Glomerular plasmin-like activity was absent or weak in normal controls and in patients with rapidly progressive glomerulonephritis, although tubulointerstitial activity was occasionally detected. Prominent glomerular plasmin-like activity was found in patients who had APSGN and in whom glomerular NAPlr was positive, whereas it was absent or weak in patients who had APSGN and in whom glomerular NAPlr was negative. The distribution of glomerular plasmin-like activity was identical to that of NAPlr deposition but was generally different from that of fibrin(ogen) deposition as assessed by double staining. The activity was abolished by the addition of aprotinin to the reaction mixture but was not altered by the addition of a matrix metalloprotease inhibitor, a cysteine protease inhibitor, or inhibitors of plasminogen activators. Thus, upregulated glomerular plasmin-like activity in relation to NAPlr deposition in APSGN was identified. This result supports the nephritogenic character of NAPlr and offers insight into the mechanism whereby this antigen induces nephritis.

show abstract

“…1-Acyl-C16 PAF (1-palmitoyl-2-acetyl-snglyceryl-3-phosphorylcholine) (1-acyl-PAF) was obtained by acetylation of 1-palmitoyl-sn-glyceryl-3-phosphorylcholine with acetic anhydride and dimethyl-aminopyridine as previously described. 20 CV 3988, a structural analog of PAF that acts as specific PAF antagonist 21 was from Takeda Chemical Industries. WEB 2170, a triazolodiazepine (hetrazepinoic) with potent and specific PAFreceptor antagonist activity, 22 was obtained from Boehringer Ingelheim KG.…”

Section: Reagentsmentioning

confidence: 99%

Thrombopoietin Stimulates Endothelial Cell Motility and Neoangiogenesis by a Platelet-Activating Factor–Dependent Mechanism

Brizzi

Battaglia

Montrucchio

et al. 1999

Circulation Research

View full text Add to dashboard Cite

—In this study, we demonstrate that human umbilical cord vein–derived endothelial cells (HUVECs) expressed c-Mpl, the thrombopoietin (TPO) receptor, and that TPO activates HUVECs in vitro, as indicated by directional migration, synthesis of 1-alkyl-/1-acyl-platelet-activating factor (PAF) and interleukin-8 (IL-8), and phosphorylation of the signal transducers and activators of transcription (STAT) STAT1 and STAT5B. The observation that WEB 2170 and CV3988, 2 structurally unrelated PAF receptor antagonists, prevented the motility of HUVECs induced by TPO suggests a role of PAF as secondary mediator. Moreover, kinetic analysis of TPO-induced tyrosine phosphorylation of STAT demonstrated that STAT5B activation temporally correlated with the synthesis of PAF. PAF, in turn, induced a rapid tyrosine phosphorylation of STAT5B and PAF receptor blockade, by WEB 2170, preventing both TPO- and PAF-mediated STAT5B activation. The in vivo angiogenic effect of TPO, studied in a mouse model of Matrigel implantation, demonstrated that TPO induced a dose-dependent angiogenic response that required the presence of heparin. Moreover, the in vivo angiogenic effect of TPO was inhibited by the PAF receptor antagonist WEB 2170 but not by the anti–basic fibroblast growth factor neutralizing antibody. These results indicate that the effects of TPO are not restricted to cells of hematopoietic lineages, because TPO is able to activate endothelial cells and to induce an angiogenic response in which the recruitment of endothelial cells is mediated by the synthesis of PAF. Moreover, biochemical analysis supports the hypothesis that STAT5B may be involved in the signaling pathway leading to PAF-dependent angiogenesis.

show abstract

Plasmin Promotes an Endothelium-Dependent Adhesion of Neutrophils

Abstract: The synthesis of PAF by endothelial cells at the site of plasmin generation and the endothelial expression of P-selectin may render the endothelial cell surface proadhesive for neutrophils and may favor a local increase in vascular permeability.

Cited by 53 publications

References 35 publications

Endogenous Tissue-Type Plasminogen Activator Is Protective duringEscherichia coli-Induced Abdominal Sepsis in Mice

Endogenous Tissue-Type Plasminogen Activator Is Protective duringEscherichia coli-Induced Abdominal Sepsis in Mice

Glomerular Plasmin-Like Activity in Relation to Nephritis-Associated Plasmin Receptor in Acute Poststreptococcal Glomerulonephritis

Thrombopoietin Stimulates Endothelial Cell Motility and Neoangiogenesis by a Platelet-Activating Factor–Dependent Mechanism

Contact Info

Product

Resources

About