Urokinase Induces Basophil Chemotaxis through a Urokinase Receptor Epitope That Is an Endogenous Ligand for Formyl Peptide Receptor-Like 1 and -Like 2

Paulis, Amato de; Montuori, Nunzia; Prevete, Nella; Fiorentino, Isabella; Rossi, Francesca Wanda; Visconte, Valeria; Rossi, Guido; Marone, Gianni; Ragno, Pia

doi:10.4049/jimmunol.173.9.5739

Cited by 99 publications

(105 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results parallel what is known about uPA as a mediator of cell migration. This serine protease is not considered a chemotactic factor [48,49]. When bound to uPAR, uPA is able to promote both cell migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Beaulieu

Church

2007

Experimental Cell Research

View full text Add to dashboard Cite

Activated protein C (APC) is a serine protease that regulates thrombin (IIa) production through inactivation of blood coagulation factors Va and VIIIa. APC also has non-hemostatic functions related to inflammation, proliferation, and apoptosis through various mechanisms. Using two breast cancer cell lines, MDA-MB-231 and MDA-MB-435, we investigated the role of APC in cell chemotaxis and invasion. Treatment of cells with increasing APC concentrations (1-50 μg/ml) increased invasion and chemotaxis in a concentration-dependent manner. Only the active form of APC increased invasion and chemotaxis of the MDA-MB-231 cells when compared to 3 inactive APC derivatives. Using a modified "checkerboard" analysis, APC was shown to only affect migration when plated with the cells; therefore, APC is not a chemoattractant. Blocking antibodies to endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1) attenuated the effects of APC on chemotaxis in the MDA-MB-231 cells. Finally, treatment of the MDA-MB-231 cells with the proliferation inhibitor, Na butyrate, showed that APC did not increase migration by increasing cell number. Therefore, APC increases invasion and chemotaxis of cells by binding to the cell surface and activating specific signaling pathways through EPCR and PAR-1.

show abstract

Section: Discussionmentioning

confidence: 99%

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Beaulieu

Church

2007

Experimental Cell Research

View full text Add to dashboard Cite

show abstract

“…Far from being an inactive degradation product, suPAR has important chemotactic properties due to its ability to bind to the G protein-coupled receptor formyl-peptide-receptor-like-1/lipoxin A4 receptor (FPRL1/LXA4R). Whether this truncated suPAR-induced signaling is mediated by the fMLP receptor homologue FPRL1 and FPRL2 is still unclear (55,56). FPRL1/LXA4R is expressed by leukocytes and epithelial cells.…”

Section: Soluble Upar (Supar): a Chemotactic Peptidementioning

confidence: 99%

“…[1] Through transactivation of uPAR co-receptors including the epidermal growth factor receptor, several integrins, and gp130, extracellular signal regulated kinase (ERK) or signal transducer and activator of transcription (STAT) signaling pathways may be activated (28,(54)(55)(56)(57). [2] The uPA-ligated cell surface uPAR may laterally interact with integrins, especially those that bind to the extracellular matrix proteins vitronectin and fibronectin (58,59).…”

Section: Receptor-ligand Interactionsmentioning

confidence: 99%

Urokinase and its receptors in chronic kidney disease

Zhang

Eddy

2008

Front Biosci

View full text Add to dashboard Cite

Since the recognition that plasminogen activator inhibitor-1 (PAI-1) is a powerful profibrotic molecule, there has been considerable interest in deciphering the extent to which this effect is mediated by its ability to inhibit serine proteases with downstream effects on fibrogenesis. This review will summarize current knowledge about the serine protease urokinase-type plasminogen activator and its high affinity receptor uPAR/CD87 as it pertains to chronic kidney disease (CKD) progression. An emerging theme is that the effects of PAI-1 and uPAR appear to be organ-and site-specific. Normal kidney tubules produce a large quantity of uPA that is secreted into the urinary space. Activity levels increase during CKD presumably due to new sources of production by macrophages and fibroblasts. By activating hepatocyte growth factor and degrading fibrinogen uPA may have anti-fibrotic effects. However CKD severity after experimental ureteral obstruction is not altered by endogenous uPA deficiency. Beneficial effects of exogenous uPA have been reported in experimental models of fibrosis in the lung and liver but CKD awaits exploration.Absent in normal kidneys uPAR is expressed by both renal parenchymal cells and inflammatory cells in a variety of pathological states. Such expression appears beneficial based on studies performed in uPAR-deficient mice. The uPAR promotes bacterial clearance in infectious diseases. In CKD uPAR expression is associated with high uPA activity but its most important effect appears to be due to scavenging activities and effects on cell recruitment and migration. Although uPAR itself is a non-signaling receptor, it interacts with a variety of co-receptors to modify cellular behavior. Best known are interactions with the low-density lipoprotein receptor-related protein (LRP-1) that lead to PAI-1 endocytosis and degradation, and interactions with several integrins to regulate matrix-dependent cell migration. Contacts with the receptor for the complement C5a component and the interleukin −6 receptor gp130 are examples of other recently recognized interactions.In addition to uPA, vitronectin and high molecular weight kininogen are alternate uPAR ligands that could be implicated in CKD progression. uPAR may also be shed from cell membranes. This soluble form (suPAR) has been detected in plasma and urine and is known to be a chemoattractant for leukocytes that express the formyl-peptide-receptor-like receptor

show abstract

“…Therefore, this study was designed: (1) to assess whether gastric epithelial cell lines express FPRs; (2) to investigate whether Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) stimulates cell migration and proliferation and VEGF expression and release in gastric epithelial cell lines; (3) to investigate the role of FPRs in any such effect(s); and (4) to evaluate whether Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) accelerates healing in a rat model of indomethacin-induced gastric mucosal damage.…”

mentioning

confidence: 99%

Helicobacter pylori Hp(2–20) Promotes Migration and Proliferation of Gastric Epithelial Cells by Interacting with Formyl Peptide Receptors In Vitro and Accelerates Gastric Mucosal Healing In Vivo

Paulis¹,

Prevete²,

Rossi³

et al. 2009

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Helicobacter pylori-derived peptide RpL1 aa 2–20 (Hp(2–20)) in addition to its antimicrobial action exerts several immunomodulatory effects in eukaryotic cells by interacting with formyl peptide receptors (FPRs). It has recently been shown that activation of FPRs facilitates intestinal epithelial cell restitution. We investigated whether Hp(2–20) induces healing of injured gastric mucosa and assessed the mechanisms underlying any such effect. We investigated the expression of FPRs in two gastric epithelial cell lines (MKN-28 and AGS) at mRNA and protein level. To determine whether FPRs were functional we performed chemotaxis experiments and proliferation assays and studied the Hp(2–20)-activated downstream signaling pathway. The effect of Hp(2–20) on mucosal healing was evaluated in rats after indomethacin-induced injury. Here we show that: (1) FPRs were expressed in both cell lines; (2) Hp(2–20) stimulated migration and proliferation of gastric epithelial cells; (3) this effect was specifically mediated by formyl peptide receptor-like 1 (FPRL1) and FPRL2 and was associated with activation of FPR-related downstream signaling pathways; (4) Hp(2–20) up-regulated the expression and secretion of vascular endothelial growth factor; and (5) Hp(2–20) accelerated healing of rat gastric mucosa after injury brought about by indomethacin at both the macroscopic and microscopic levels. In conclusion, by interacting with FRPL1 and FPRL2, H. pylori-derived Hp(2–20) induces cell migration and proliferation, as well as the expression of vascular endothelial growth factor, thereby promoting gastric mucosal healing. This study provides further evidence of the complexity of the relationship between H. pylori and human gastric mucosa, and it suggests that a bacterial product may be used to heal gastric mucosal injury.

show abstract

Urokinase Induces Basophil Chemotaxis through a Urokinase Receptor Epitope That Is an Endogenous Ligand for Formyl Peptide Receptor-Like 1 and -Like 2

Cited by 99 publications

References 64 publications

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Urokinase and its receptors in chronic kidney disease

Helicobacter pylori Hp(2–20) Promotes Migration and Proliferation of Gastric Epithelial Cells by Interacting with Formyl Peptide Receptors In Vitro and Accelerates Gastric Mucosal Healing In Vivo

Contact Info

Product

Resources

About