Effect of β‐Adrenergic Agents on Human Neutrophil Granulocyte Activation with N‐Formyl‐methionyl‐leucyl‐phenylalanine and Phorbol Myristate Acetate

Opdahl, Helge; Benestad, Haakon B.; Nicolaysen, Gunnar

doi:10.1111/j.1600-0773.1993.tb01640.x

Cited by 14 publications

(9 citation statements)

References 35 publications

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“…These results have been corroborated by other groups using cardiomyocyte models of cardiomyopathy and heart failure, suggesting that the ROS-␤ 2 AR link is physiologically significant and, if unregulated, may be involved in pathophysiological states (Li et al, 2010;Xu et al, 2011). It is noteworthy that the agonism of ␤ 2 AR in human neutrophils facilitates a decrease in formyl-Met-Leu-Phe-mediated ROS generation (Opdahl et al, 1993;Anderson et al, 1996;Barnett et al, 1997), and others have shown that ␤ 2 AR agonism specifically decreases only extracellular ROS from these cells (Kopprasch et al, 1997). Together, these results suggest that ␤ 2 AR agonism may have cell type-specific differential effects on modulating ROS levels.…”

Section: Introductionsupporting

confidence: 75%

Agonist- and Hydrogen Peroxide-Mediated Oxidation of the β₂Adrenergic Receptor: Evidence of Receptor S-Sulfenation as Detected by a Modified Biotin-Switch Assay

Burns

Moniri²

2011

J Pharmacol Exp Ther

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Reactive oxygen species (ROS), including hydrogen peroxide (H 2 O 2 ), have recently been shown to be generated upon agonism of several members of the G protein-coupled receptor (GPCR) superfamily, including ␤ 2 -adrenergic receptors (␤ 2 ARs). Previously, we have demonstrated that inhibition of intracellular ROS generation mitigates ␤ 2 AR signaling, suggesting that ␤ 2 AR-mediated ROS generation is capable of feeding back to regulate receptor function. Given that ROS, specifically H 2 O 2 , are able to post-translationally oxidize protein cysteine sulfhydryls to cysteine-sulfenic acids, the goal of the current study was to assess whether ROS are capable of S-sulfenating ␤ 2 AR. Using a modified biotin-switch assay that is selective for cysteine-sulfenic acids, our results demonstrate for the first time that H 2 O 2 treatment facilitates S-sulfenation of transiently overexpressed ␤ 2 AR in human embryonic kidney 293 cells. It is noteworthy that stimulation of cells with the ␤-agonist isoproterenol produces both dose-and time-dependent S-sulfenation of ␤ 2 AR, an effect that is receptor-dependent, and demonstrates that receptor-generated ROS are also capable of oxidizing the ␤ 2 AR. Receptor-dependent S-sulfenation was inhibited by the chemoselective sulfenic acid alkylator dimedone and the cysteine antioxidant N-acetyl-L-cysteine. Moreover, our results reveal that receptor oxidation occurs in cells that endogenously express physiologically relevant levels of ␤ 2 AR, because treatment of human alveolar epithelial A549 cells with either H 2 O 2 or the ␤ 2 -selective agonist formoterol promoted receptor S-sulfenation. These findings provide the first evidence, to our knowledge, that a mammalian GPCR can be oxidized by S-sulfenation and signify an important first step toward shedding light on the overlooked role of ROS in the regulation of ␤ 2 AR function.

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Section: Introductionsupporting

confidence: 75%

Agonist- and Hydrogen Peroxide-Mediated Oxidation of the β₂Adrenergic Receptor: Evidence of Receptor S-Sulfenation as Detected by a Modified Biotin-Switch Assay

Burns

Moniri²

2011

J Pharmacol Exp Ther

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“…Theoretically, the use of drugs acting as 2 -adrenoceptor agonists might be a rational approach to control the excessive oxidant production, by stimulating the natural catecholaminedependent regulation of neutrophil activity. Although isoproterenol has been shown to inhibit the neutrophil respiratory burst [12,13], the widely used 2 -agonist salbutamol appears to be ineffective, at least using macrophages [14]. Moreover, the recently developed long-acting 2 -agonist salmeterol [15], possibly endowed with potential anti-inflammatory properties [16], was found to be incapable of inhibiting the respiratory burst in guinea pig eosinophils [17].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of salmeterol on the respiratory burst of adherent human neutrophils

Ottonello

Morone

Dapino

et al. 1996

Clinical and Experimental Immunology

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SUMMARYHuman neutrophils, plated in fibronectin-coated wells and stimulated with N-formyl-methionyl-leucylphenylalanine (fMLP), were found to undergo a massive and prolonged respiratory burst, as measured by monitoring superoxide production. The 2 -agonist salmeterol inhibited the respiratory burst in a dose-dependent manner. In contrast, salbutamol was ineffective. Moreover, the neutrophil respiratory burst was partially suppressed by prostaglandin E 2 (PGE 2 ) and the phosphodiesterase type IV (PDE-IV) inhibitor RO 20-1724. When salmeterol was used in combination with PGE 2 or RO 20-1724, additive inhibitory effects were observed. The inhibitory activity of salmeterol was not reversed in the presence of the -blocker propranolol, and did not correlate with its ability of increasing cyclic AMP (cAMP) levels. Finally, the compounds used did not affect neutrophil adherence to fibronectin-coated wells. The results suggest that salmeterol is capable of down-regulating the neutrophil oxidative response to fMLP, also of co-operating with PGE 2 and PDE-IV inhibitor RO 20-1724 in a manner not related to its 2 -receptor binding activity. In other words, salmeterol displays neutrophil-directed effects, susceptible to be amplified by natural mediators such as PGE 2 or PDE-IV inhibitors, consistent with possible anti-inflammatory properties of the drug.

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“…12 In animal models of acute lung injury, b 2 -agonists reduce pulmonary neutrophil sequestration. 13 14 In vitro b 2agonists reduce the production of oxygen free radicals from neutrophils and other inflammatory cells 15 16 and reduce inflammatory cytokine production. 17 In humans, inhaled salmeterol (long-acting b 2 -agonist) inhibited LPS-induced neutrophil influx, degranulation and tumour necrosis factor (TNF)a release.…”

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In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury

Perkins

Nathani

McAuley

et al. 2007

Thorax

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Background: Intravenous salbutamol (albuterol) reduces lung water in patients with the acute respiratory distress syndrome (ARDS). Experimental data show that it also reduces pulmonary neutrophil accumulation or activation and inflammation in ARDS. Aim: To investigate the effects of salbutamol on neutrophil function. Methods: The in vitro effects of salbutamol on neutrophil function were determined. Blood and bronchoalveolar lavage (BAL) fluid were collected from 35 patients with acute lung injury (ALI)/ARDS, 14 patients at risk from ARDS and 7 ventilated controls at baseline and after 4 days' treatment with placebo or salbutamol (ALI/ARDS group). Alveolar-capillary permeability was measured in vivo by thermodilution (PiCCO). Neutrophil activation, adhesion molecule expression and inflammatory cytokines were measured. Results: In vitro, physiological concentrations of salbutamol had no effect on neutrophil chemotaxis, viability or apoptosis. Patients with ALI/ARDS showed increased neutrophil activation and adhesion molecule expression compared with at risk-patients and ventilated controls. There were associations between alveolarcapillary permeability and BAL myeloperoxidase (r = 0.4, p = 0.038) and BAL interleukin 8 (r = 0.38, p = 0.033). In patients with ALI/ARDS, salbutamol increased numbers of circulating neutrophils but had no effect on alveolar neutrophils. Conclusion: At the onset of ALI/ARDS, there is increased neutrophil recruitment and activation. Physiological concentrations of salbutamol did not alter neutrophil chemotaxis, viability or apoptosis in vitro. In vivo, salbutamol increased circulating neutrophils, but had no effect on alveolar neutrophils or on neutrophil activation. These data suggest that the beneficial effects of salbutamol in reducing lung water are unrelated to modulation of neutrophil-dependent inflammatory pathways.

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Effect of β‐Adrenergic Agents on Human Neutrophil Granulocyte Activation with N‐Formyl‐methionyl‐leucyl‐phenylalanine and Phorbol Myristate Acetate

Cited by 14 publications

References 35 publications

Agonist- and Hydrogen Peroxide-Mediated Oxidation of the β₂Adrenergic Receptor: Evidence of Receptor S-Sulfenation as Detected by a Modified Biotin-Switch Assay

Agonist- and Hydrogen Peroxide-Mediated Oxidation of the β₂Adrenergic Receptor: Evidence of Receptor S-Sulfenation as Detected by a Modified Biotin-Switch Assay

Inhibitory effect of salmeterol on the respiratory burst of adherent human neutrophils

In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury

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Effect of β‐Adrenergic Agents on Human Neutrophil Granulocyte Activation with N‐Formyl‐methionyl‐leucyl‐phenylalanine and Phorbol Myristate Acetate

Cited by 14 publications

References 35 publications

Agonist- and Hydrogen Peroxide-Mediated Oxidation of the β2Adrenergic Receptor: Evidence of Receptor S-Sulfenation as Detected by a Modified Biotin-Switch Assay

Agonist- and Hydrogen Peroxide-Mediated Oxidation of the β2Adrenergic Receptor: Evidence of Receptor S-Sulfenation as Detected by a Modified Biotin-Switch Assay

Inhibitory effect of salmeterol on the respiratory burst of adherent human neutrophils

In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury

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Agonist- and Hydrogen Peroxide-Mediated Oxidation of the β₂Adrenergic Receptor: Evidence of Receptor S-Sulfenation as Detected by a Modified Biotin-Switch Assay

Agonist- and Hydrogen Peroxide-Mediated Oxidation of the β₂Adrenergic Receptor: Evidence of Receptor S-Sulfenation as Detected by a Modified Biotin-Switch Assay