Effects of Jarastatin, a Novel Snake Venom Disintegrin, on Neutrophil Migration and Actin Cytoskeleton Dynamics

Coelho, Ana Lúcia; Freitas, Marta Sampaio de; Oliveira-Carvalho, Ana Lúcia; Moura‐Neto, Vivaldo; Zingali, Russolina B.; Barja‐Fidalgo, Christina

doi:10.1006/excr.1999.4583

Cited by 58 publications

(54 citation statements)

References 42 publications

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“…23 Erythrocytes were removed by hypotonic lysis, and PMNs were resuspended in RPMI-1640 medium (Sigma) or Dulbecco modified Eagle medium (DMEM). Neutrophil purity and viability were always higher than 99% and 96%, respectively.…”

Section: Human Neutrophil Isolationmentioning

confidence: 99%

Neutrophil activation by heme: implications for inflammatory processes

Graça-Souza

Arruda

Freitas

et al. 2002

Blood

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262

218

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Heme, a ubiquitous iron-containing compound, is present in large amounts in many cells and is inherently dangerous, particularly when it escapes from intracellular sites. The release of heme from damaged cells and tissues is supposed to be higher in diseases such as malaria and hemolytic anemia or in trauma and hemorrhage. We investigated here the role of free ferriprotoporphyrin IX (hemin) as a proinflammatory molecule, with particular attention to its ability to activate neutrophil responses. Injecting hemin into the rat pleural cavity resulted in a dosedependent migration of neutrophils, indicating that hemin is able to promote the recruitment of these cells in vivo. In vitro, hemin induced human neutrophil chemotaxis and cytoskeleton reorganization, as revealed by the increase of neutrophil actin polymerization. Exposure of human neutrophils to 3 M hemin activated the expression of the chemokine interleukin-8, as demonstrated by quantitative reverse-transcription polymerase chain reaction, indicating a putative molecular mechanism by which hemin induces chemotaxis in vivo. Brief incubation of human neutrophils with micromolar concentrations of hemin (1-20 M) triggered the oxidative burst, and the production of reactive oxygen species was directly proportional to the concentration of hemin added to the cells. Finally, we observed that human neutrophil protein kinase C was activated by hemin in vitro, with a K 1/2 of 5 M. Taken IntroductionHeme released from hemeproteins has been shown to promote the formation of oxygen radicals, playing a role as a catalyst in the oxidation of lipids, proteins, and DNA. [1][2][3] In addition, free heme can promptly bind to and oxidize low-density lipoprotein, acting as a biologically relevant lipoprotein oxidant. 4 Hemoglobin (probably because of the release of free heme and heme iron) may contribute to the acute renal failure often seen after episodes of intravascular hemolysis. 5,6 In fact, it has been proposed that heme could be considered one causative agent in organ failure after ischemia-reperfusion because heme-oxygenase is induced in heart and kidney. 7 In normal conditions, diverse species produce avid hemebinding plasma proteins, such as hemopexin, that efficiently remove most of the heme produced intravascularly, 8 thus preventing nonspecific cellular heme uptake and heme-catalyzed oxidation reactions. However, pathologic situations of increased hemolysis can lead to very high levels of free heme, as in malaria, 9 sickle cell disease, 10 HELLP (hemolysis, elevated liver levels, and low platelet count) syndrome, 11 or regions with turbulent blood flow. 12 Very little work has been done to assess the consequences of the interaction of free heme with intact cells. It has been demonstrated that free heme is promptly incorporated into endothelial cells in vitro and that this association potentiates the oxidative damage induced by chemical agents. 13 It is interesting to note that patients suffering from sickle cell disease often exhibit a low-grade chronic inflammation...

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Section: Human Neutrophil Isolationmentioning

confidence: 99%

Neutrophil activation by heme: implications for inflammatory processes

Graça-Souza

Arruda

Freitas

et al. 2002

Blood

Self Cite

262

218

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“…JT inhibited neutrophil migration induced in vivo by carrageenan injection in mice, as well as human neutrophil chemotaxis induced in vitro by distinct chemoattractants such as IL-8 and fMLP (56). Interestingly, this peptide presents a significant chemotactic activity for human neutrophils and induces homologous and heterologous desensitization to other chemotactic agents such as IL-8 or fMLP (56). The chemotactic effect of JT was inhibited by anti-α M antibodies, suggesting the involvement of Mac-1 integrin in this effect (57).…”

Section: Leukocytes and Disintegrinsmentioning

confidence: 95%

“…The chemotactic effect of JT was inhibited by anti-α M antibodies, suggesting the involvement of Mac-1 integrin in this effect (57). Neutrophil migration induced by JT in vitro is accompanied by profound alterations in the actin network, with an increase in filamentous actin (56). Migration and actin polymerization induced by JT in human neutrophils were completely inhibited by tyrosine kinase inhibitors.…”

Section: Leukocytes and Disintegrinsmentioning

confidence: 97%

“…Studying the effect of RGD-disintegrin on human neutrophils, we recently identified a unique monomeric RGD-disintegrin isolated from Bothrops jararaca venom, jarastatin (JT), which is able to bind to α M ß 2 integrin on neutrophils (56,57). JT inhibited neutrophil migration induced in vivo by carrageenan injection in mice, as well as human neutrophil chemotaxis induced in vitro by distinct chemoattractants such as IL-8 and fMLP (56).…”

Section: Leukocytes and Disintegrinsmentioning

confidence: 99%

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Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

Barja‐Fidalgo

Coelho

Saldanha-Gama

et al. 2005

Braz J Med Biol Res

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Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrinmediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp) motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrinmediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

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“…The most common agonist/platelet combination used is adenosine diphosphate (ADP) and platelet-rich plasma (PRP). Some authors standardized the platelet concentration used (Huang et al, 1991d;Marrakchi et al, (IC 50 ) within the range shown <400 nM 400-1000 nM >1000 nM Accutin (h) (Yeh et al, 1998) Applaggin (h) (Chao et al, 1989) Bitistatin (h) (Huang et al, 1991d) Cerastatin (h, r) (Marrakchi et al, 1997) Contortrostatin (h) (Kamiguti et al, 1997) Crotavirin (h) (Liu et al, 1995) Echistatin (h) TW Eristostatin (h) TW Flavostatin (h) (Kawasaki et al, 1996;Maruyama et al, 1997) Gabonin (h) (Huang et al, 1992) Jerdonatin (h) (Zhou et al, 2004) Kistrin (h) (Dennis et al, 1990) Triflavin (h) (Huang et al, 1991b) Ussuristatin 1 (h) (Oshikawa and Terada, 1999) Ussuristatin 2 (h) (Oshikawa and Terada, 1999) Bitistatin (h) (Huang et al, 1991d) Halysetin (h) (Liu et al, 2000) Halysin (h) (Huang et al, 1991a) Jarastatin (r) (Coelho et al, 1999) Testing reported from human (h) or rabbit (r) platelets. Disintegrins in more than one column showed differences based on the species or preparation of platelet used (washed, gel-filtered, or platelet-rich plasma).…”

Section: Variability In Potencymentioning

confidence: 99%

Monomeric and Dimeric Disintegrins: Platelet Active Agents From Viper Venom

et al. 2007

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When the term "disintegrin" was first coined in 1990, it described a family of naturally occurring proteins with low molecular weights and highly conserved sequences, both in their cysteine arrangements and adhesive Arg-Gly-Asp (RGD) motifs. Another common characteristic was the inhibitory potential these proteins demonstrated in interacting with cell-surface integrin receptors. Measurement of the effect by disintegrins on the interaction between the platelet receptor αIIbβ3 and its ligand, fibrinogen, has become a hallmark assay for comparing the activities of members of this increasingly diverse family discovered in the past two decades. This review focuses on the inhibitory profiles, based on platelet function, of the monomeric and heterodimeric disintegrins described to date, as well as the informative contributions of disintegrin mutations in our understanding

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Effects of Jarastatin, a Novel Snake Venom Disintegrin, on Neutrophil Migration and Actin Cytoskeleton Dynamics

Cited by 58 publications

References 42 publications

Neutrophil activation by heme: implications for inflammatory processes

Neutrophil activation by heme: implications for inflammatory processes

Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

Monomeric and Dimeric Disintegrins: Platelet Active Agents From Viper Venom

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