Angiotensin II Induces Neutrophil Accumulation In Vivo Through Generation and Release of CXC Chemokines

Nabah, Yafa Naim Abu; Mateo, Teresa; Estellés, Rossana; Mata, Manuel; Zagorski, John; Sarau, Henry M.; Cortijo, Julio; Morcillo, Esteban J.; Jose, Peter J.; Sanz, María-Jesús

doi:10.1161/01.cir.0000148824.93600.f3

Cited by 113 publications

(90 citation statements)

References 24 publications

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“…2 for review). Consistent with the latter finding, blockade of AT 1 , the major receptor mediating the inflammatory actions of Ang II, reduces neutrophil recruitment and cytokine release in models of inflammation (12,37,38). However, to our knowledge, the expression of Mas receptor in periarticular tissues was demonstrated for the first time in the present study.…”

Section: Discussionsupporting

confidence: 91%

“…In addition to inhibiting neutrophil influx due to the inhibition of local production of chemokines, it was possible that Mas agonists could be directly interfering with the process of leukocyte-endothelial cell interaction, hence preventing their influx. In support of the latter possibility, other studies have found that Ang II via AT 1 receptor stimulated leukocyte-endothelium interactions and increased neutrophil migration in vivo (37,38). In our study, treatment with the Mas receptor agonist AVE 0991 significantly inhibited rolling and cell adhesion of leukocytes to endothelial cells in the joint microvasculature of mice subjected to AIA.…”

Section: Discussionsupporting

confidence: 87%

“…Such inhibition could account for the local inhibition of neutrophil influx. However, a few studies have shown that components of the RAS may affect leukocyte recruitment directly by affecting leukocyteendothelial cell interactions (37,38). To evaluate whether activation of the Mas receptor would affect leukocyte-endothelium interactions in vivo, we used an intravital microscopy strategy in which AVE 0991 was given to mice much after immunization and challenge but just prior to the intravital procedures (Fig.…”

Section: Anti-inflammatory Mechanisms Of Ave 0991 Treatmentmentioning

confidence: 99%

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Anti-Inflammatory Effects of the Activation of the Angiotensin-(1–7) Receptor, Mas, in Experimental Models of Arthritis

Sachs¹

2010

The Journal of Immunology

160

107

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Activation of the renin-angiotensin (Ang) system induces inflammation via interaction between Ang II and type 1 receptor on leukocytes. The relevance of the new arm of the renin-Ang system, namely Ang-converting enzyme-2/Ang-(1–7)/Mas receptor, for inflammatory responses is not known and was investigated in this study. For this purpose, two experimental models were used: Ag-induced arthritis (AIA) in mice and adjuvant-induced arthritis (AdIA) in rats. Male C57BL/6 wild-type or Mas−/− mice were subjected to AIA and treated with Ang-(1–7), the Mas agonist AVE 0991, or vehicle. AdIA was performed in female rats that were given AVE 0991 or vehicle. In wild-type mice, Mas protein is expressed in arthritic joints. Administration of AVE 0991 or Ang-(1–7) decreased AIA-induced neutrophil accumulation, hypernociception, and production of TNF-α, IL-1β, and CXCL1. Histopathological analysis showed significant reduction of inflammation. Mechanistically, AVE 0991 reduced leukocyte rolling and adhesion, even when given after Ag challenge. Mas−/− mice subjected to AIA developed slightly more pronounced inflammation, as observed by greater neutrophil accumulation and cytokine release. Administration of AVE 0991 was without effect in Mas−/− mice subjected to AIA. In rats, administration of AVE 0991 decreased edema, neutrophil accumulation, histopathological score, and production of IL-1β and CXCL1 induced by AdIA. Therefore, activation of Mas receptors decreases neutrophil influx and cytokine production and causes significant amelioration of arthritis in experimental models of arthritis in rats and mice. This approach might represent a novel therapeutic opportunity for arthritis.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 87%

Section: Anti-inflammatory Mechanisms Of Ave 0991 Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

Anti-Inflammatory Effects of the Activation of the Angiotensin-(1–7) Receptor, Mas, in Experimental Models of Arthritis

Sachs¹

2010

The Journal of Immunology

160

107

View full text Add to dashboard Cite

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“…This was mediated by acceleration of macrophage infiltration and necrotic re-absorption. The action of the RAAS in mobilization of inflammatory cells also involves Ang II mediated facilitation of chemokines release, which leads to neutrophil recruitment, as previously described by Nabah et al (37). These effects may contribute to increased neutrophil infiltration into ischemic myocardium, an action that can lead to an abnormal inflammatory response and acute ventricular expansion.…”

Section: The Cardiac Renin-angiotensin-aldosterone Systemmentioning

confidence: 61%

Remodeling in the ischemic heart: the stepwise progression for heart

Mill¹,

Stefanon

Santos

et al. 2011

Braz J Med Biol Res

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Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI) has decreased in the last decades. However, the incidence of heart failure (HF) in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

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“…55 Classically, chronic RAS activation through AT1R leads to increased blood pressure, renal salt retention, aldosterone release and sympathetic nervous system activation. 56 Locally, stimulation of RASs may influence diverse physiological outputs, especially inflammatory processes through AT1R-mediated stimulation of neutrophil migration 57 and activation of the pro-inflammatory effector NF-κB (nuclear factor-κB) in phagocytes, 58 amongst others. AT1R blockers were effective in counteracting the deleterious inflammatory responses elicited by some bacterial infections, including acute respiratory distress syndrome (ARDS) triggered by Bordetella bronchiseptica 59 and lung colonization by P. aeruginosa.…”

Section: Functional Tests On the Selected Compounds From The Virtual mentioning

confidence: 99%

Identification of Anti-Inflammatory and Anti-Hypertensive Drugs as Inhibitors of Bacterial Diguanylate Cyclases

Wiggers¹,

Crusca²,

Silva³

et al. 2017

J. Braz. Chem. Soc.

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Biofilms are widely present in many human chronic infections, often more resistant to treatment with antibiotics. Bacterial diguanylate cyclases (DGCs) synthesize cyclic dimeric guanosine monophosphate (c-di-GMP) from two guanosine-5'-triphosphate (GTP) molecules. c-di-GMP is a central second messenger controlling biofilm formation, turning this class of enzymes an attractive target to prevent and disrupt biofilms of pathogenic bacteria. Here, we apply an in silico ligand-and target-based hybrid method to screen potential DGC inhibitors from an FDA-approved drug databank. Mass spectrometry assays confirmed that seven screened compounds selectively bound to the GTP active site of P. aeruginosa WspR GGDEF domain. Four out of those, including the anti-inflammatory sulfasalazine and the anti-hypertensive eprosartan, inhibited distinct DGCs (P. aeruginosa WspR and E. coli YdeH) in the micromolar range. Sulfasalazine and eprosartan reduced aggregation in solution of E. coli overexpressing WspR or YdeH. Similar anti-aggregation effects were also observed for sulfasalazine-related anti-inflammatory drugs sulfadiazine and sulfathiazole, the latter a previously described anti-biofilm agent. The optimized pharmacokinetic properties and toxicological profiles of the DGC inhibitors could be promising candidates for new anti-microbial agents based on the drug reposition strategy.Keywords: c-di-GMP, diguanylate cyclase enzymes, bacterial biofilm, virtual screening, drug repositioning IntroductionBacterial biofilms, a multicellular community encased in an extracellular matrix, are commonly related to persistent infections, usually less susceptible to antibiotic treatments when compared to planktonic cells. [1][2][3] According to the National Institute of Health, 4 up to 80% of human bacterial infections involve biofilm-associated microorganisms. For instance, biofilm formation plays a crucial role in microbe pathogenicity such as Legionnaire's disease, endocarditis, pneumonia accompanied by cystic fibrosis and infections of urogenital and gastrointestinal tracts. 5,6 Furthermore, biofilm infections promote devastating effects on medical device implanted and immunocompromised individuals, representing a major medical and economic predicament. 7 The burden on public health due to chronic biofilm contaminations urge for the development of new chemotherapeutic approaches. Cellular processes controlling biofilm formation and dispersion, such as quorum sensing systems and metabolic pathways, are important targets for the discovery of new bioactive compounds. 8-10The second messenger bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a key regulator of bacterial behavior, especially controlling the switch between the motile planktonic and sedentary biofilm-associated lifestyles. Cyclic di-GMP stimulates the biosynthesis of adhesins and exopolysaccharide matrix substances in biofilms and inhibits various forms of motility. In general, low intracellular c-di-GMP levels are associated with freeswimming cells, whereas bacter...

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Angiotensin II Induces Neutrophil Accumulation In Vivo Through Generation and Release of CXC Chemokines

Cited by 113 publications

References 24 publications

Anti-Inflammatory Effects of the Activation of the Angiotensin-(1–7) Receptor, Mas, in Experimental Models of Arthritis

Anti-Inflammatory Effects of the Activation of the Angiotensin-(1–7) Receptor, Mas, in Experimental Models of Arthritis

Remodeling in the ischemic heart: the stepwise progression for heart

Identification of Anti-Inflammatory and Anti-Hypertensive Drugs as Inhibitors of Bacterial Diguanylate Cyclases

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