Heterologous desensitization of IL-8-mediated chemotaxis in human neutrophils by a cell-binding fragment of fibronectin

Stanton, K. J.; Frewin, Mary Beth; Gudewicz, Paul W.

doi:10.1002/jlb.65.4.515

Cited by 15 publications

(9 citation statements)

References 41 publications

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“…Thus, our results indicate that Alt-C may interact with adhesive receptors on the neutrophil surface inducing cell activation and leading to desensitization of the receptor to other chemotactic stimuli after prior stimulation. These findings are in agreement with previous studies describing that neutrophil migration can be inhibited or desensitized to a given chemoattractant by prior exposure to the same agonist (homologous desensitization) or to unrelated chemotactic factors (heterologous desensitization) [20,29].…”

Section: Discussionsupporting

confidence: 93%

Alternagin‐C, a nonRGD‐disintegrin, induces neutrophil migration via integrin signaling

Mariano-Oliveira

Coelho

Terruggi

et al. 2003

European Journal of Biochemistry

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Recently, a new protein containing a disintegrin domain, alternagin-C (Alt-C), was purified from Bothrops alternatus venom. Unlike other disintegrins, in Alt-C an ECD amino acid motif takes the place of the RGD sequence. Most disintegrins contain an RGD/KGD sequence and are very potent inhibitors of platelet aggregation, as well as other cell interactions with the extracellular matrix, including tumor cell metastasis and angiogenesis. The present study investigated the effects of Alt-C on human neutrophil chemotaxis in vitro and the activation of integrin-mediated pathways. Alt-C showed a potent chemotactic effect for human neutrophils when compared to N-formyl-methionyl-leucylphenylalanine peptide (fMLP), a classic chemotactic agent. Moreover, preincubation of neutrophils with Alt-C significantly inhibited chemotaxis toward fMLP and itself. In addition, a peptide containing an ECD sequence presented a chemotactic activity and significantly inhibited chemotaxis induced by Alt-C and fMLP. A significant increase of F-actin content was observed in cells treated with Alt-C, showing that the chemotactic activity of Alt-C on neutrophils is driven by actin cytoskeleton dynamic changes. Futhermore, this protein was able to induce an increase of phosphotyrosine content triggering focal adhesion kinase activation and its association with phosphatidylinositol 3-kinase. Alt-C was also able to induce a significant increase in extracellular signal-regulated kinase 2 1 nuclear translocation. The chemotactic activity of Alt-C was partially inhibited by LY294002, a specific phosphatidylinositol 3-kinase inhibitor, and by PD98056, a Map kinase kinase 2 inhibitor. These findings suggest that Alt-C can trigger human neutrophil chemotaxis modulated by intracellular signals characteristic of integrin-activated pathways and that these effects could be related to the ECD motif present in disintegrin-like domain.Keywords: neutrophil; chemotaxis; integrin signaling.The recruitment of polymorphonuclear neutrophils to sites of inflammation and tissue injury requires rolling on the vessel walls and subsequent migration through the vascular endothelium. Migration involves multiple neutrophil adhesion receptors, such as L-selectin for rolling and integrins for adherence and locomotion [1,2]. These adhesion receptors have counter-receptors on endothelial cells and also specific ligands that are extracellular matrix (ECM) proteins [3].Integrins are comprised of noncovalently linked a and b chains that can associate in various combinations and thus determine the ligand-binding specificities of the intact heterodimer [4,5]. On the other hand, binding of integrins to the ECM is mediated by an integrin-recognition RGD motif found on some ECM components such as fibronectin, vitronectin and fibrinogen [6]. Integrin-ligand binding and receptor clustering initiate a signaling cascade that involves receptor activation, increase in tyrosine kinase activity and protein phosphorylation, and reorganization of the actin cytoskeleton [5,7]. Focal adhesion kin...

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Section: Discussionsupporting

confidence: 93%

Alternagin‐C, a nonRGD‐disintegrin, induces neutrophil migration via integrin signaling

Mariano-Oliveira

Coelho

Terruggi

et al. 2003

European Journal of Biochemistry

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“…This positive stimulation induced by JT may be responsible for its partial inhibitory effect on chemotaxis, compared with the full inhibition caused by KR and FL. The inhibition of a chemotactic effect by prior exposure to the agonist or to selected structurally unrelated chemotactic factors has already been described for known PMN activators (homologous or heterologous desensitization) (26). Homologous desensitization induced by JT was reported previously (14).…”

Section: Discussionmentioning

confidence: 77%

Interaction of disintegrins with human neutrophils induces cytoskeleton reorganization, focal adhesion kinase activation, and extracellular‐regulated kinase‐2 nuclear translocation, interfering with the chemotactic function

et al. 2001

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We previously demonstrated that jarastatin (JT), a new disintegrin from Bothrops jararaca venom, altered actin dynamics in human polymorphonuclear neutrophils (PMNs) and inhibited cell migration in vivo and in vitro (14). In this study, we evaluated the effects of JT and two other monomeric disintegrins, kistrin (KR) and flavoridin (FL), on PMN chemotaxis and chemokinesis in vitro and on the activation of integrin‐mediated pathways. Although JT, but not KR or FL, was chemotactic, only KR was chemokinetic to PMN. However, preincubation of PMN with any disintegrins inhibited chemotaxis for fMLP. Treatment of PMN with JT and KR increased actin polymerization, whereas FL reduced the content of F‐actin. The effects of JT and KR on actin dynamics were inhibited (50%) by genistein, a tyrosine kinase inhibitor. Accordingly, JT and KR induced an increase in tyrosine phosphorylation, whereas FL had no effect. The three disintegrins were able to induce focal adhesion kinase activation. However, JT and KR promoted Erk‐2 nuclear translocation, and FL inhibited Erk‐2 activation. The data suggest that although the disintegrins JT and KR directly activate integrin‐coupled signaling, FL may interact differently with integrins, triggering an inhibitory pathway modulated by focal adhesion kinase activation.

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“…IPA pathway analysis of the commonly and differentially expressed proteins revealed that extracellular matrix proteins such as fibronectin were involved in the ILK (Integrin linked kinase) pathway. The binding of the fibronectin peptide could augment integrin signaling [64,65] during fertilization. Furthermore, Ingenuity Canonical Pathway (ICP) analysis showed that FN1 was involved in ILK signaling in the ROS- group and that this process may have been absent in the ROS+ group due to the absence of fibronectin.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of seminal fluid from men exhibiting oxidative stress

Sharma

Agarwal

Mohanty

et al. 2013

Reprod Biol Endocrinol

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BackgroundSeminal plasma serves as a natural reservoir of antioxidants. It helps to remove excessive formation of reactive oxygen species (ROS) and consequently, reduce oxidative stress. Proteomic profiling of seminal plasma proteins is important to understand the molecular mechanisms underlying oxidative stress and sperm dysfunction in infertile men.MethodsThis prospective study consisted of 52 subjects: 32 infertile men and 20 healthy donors. Once semen and oxidative stress parameters were assessed (ROS, antioxidant concentration and DNA damage), the subjects were categorized into ROS positive (ROS+) or ROS negative (ROS-). Seminal plasma from each group was pooled and subjected to proteomics analysis. In-solution digestion and protein identification with liquid chromatography tandem mass spectrometry (LC-MS/MS), followed by bioinformatics analyses was used to identify and characterize potential biomarker proteins.ResultsA total of 14 proteins were identified in this analysis with 7 of these common and unique proteins were identified in both the ROS+ and ROS- groups through MASCOT and SEQUEST analyses, respectively. Prolactin-induced protein was found to be more abundantly present in men with increased levels of ROS. Gene ontology annotations showed extracellular distribution of proteins with a major role in antioxidative activity and regulatory processes.ConclusionsWe have identified proteins that help protect against oxidative stress and are uniquely present in the seminal plasma of the ROS- men. Men exhibiting high levels of ROS in their seminal ejaculate are likely to exhibit proteins that are either downregulated or oxidatively modified, and these could potentially contribute to male infertility.

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Heterologous desensitization of IL-8-mediated chemotaxis in human neutrophils by a cell-binding fragment of fibronectin

Cited by 15 publications

References 41 publications

Alternagin‐C, a nonRGD‐disintegrin, induces neutrophil migration via integrin signaling

Alternagin‐C, a nonRGD‐disintegrin, induces neutrophil migration via integrin signaling

Interaction of disintegrins with human neutrophils induces cytoskeleton reorganization, focal adhesion kinase activation, and extracellular‐regulated kinase‐2 nuclear translocation, interfering with the chemotactic function

Proteomic analysis of seminal fluid from men exhibiting oxidative stress

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