The neutrophil chemoattractant peptide proline-glycine-proline is associated with acute respiratory distress syndrome

Sharma, Nirmal; Lal, Charitharth Vivek; Li, Jindong; Lou, Xiang‐Yang; Viera, Liliana; Abdallah, Tarek; King, R. Glenn; Sethi, Jaskaran; Kanagarajah, Prashanth; Restrepo‐Jaramillo, Ricardo; Conniff, Amanda Sales; Wei, Shi; Jackson, Patricia L.; Blalock, J. Edwin; Gaggar, Amit; Xu, Xin

doi:10.1152/ajplung.00308.2017

Cited by 22 publications

(22 citation statements)

References 52 publications

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“…Our healthy controls did not have Ac-PGP measurements. Nevertheless, our previous studies have shown absent or extremely low levels of Ac-PGP in healthy lung airway fluid [64]. It has been reported that BAL samples obtained from separate geographic regions within the same lung can demonstrate highly dissimilar microbial communities [33,65].…”

Section: Discussionmentioning

confidence: 82%

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Differences in airway microbiome and metabolome of single lung transplant recipients

et al. 2020

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Background: Recent studies suggest that alterations in lung microbiome are associated with occurrence of chronic lung diseases and transplant rejection. To investigate the host-microbiome interactions, we characterized the airway microbiome and metabolome of the allograft (transplanted lung) and native lung of single lung transplant recipients. Methods: BAL was collected from the allograft and native lungs of SLTs and healthy controls. 16S rRNA microbiome analysis was performed on BAL bacterial pellets and supernatant used for metabolome, cytokines and acetylated proline-glycine-proline (Ac-PGP) measurement by liquid chromatography-high-resolution mass spectrometry. Results: In our cohort, the allograft airway microbiome was distinct with a significantly higher bacterial burden and relative abundance of genera Acinetobacter & Pseudomonas. Likewise, the expression of the pro-inflammatory cytokine VEGF and the neutrophil chemoattractant matrikine Ac-PGP in the allograft was significantly higher. Airway metabolome distinguished the native lung from the allografts and an increased concentration of sphingosine-like metabolites that negatively correlated with abundance of bacteria from phyla Proteobacteria. Conclusions: Allograft lungs have a distinct microbiome signature, a higher bacterial biomass and an increased Ac-PGP compared to the native lungs in SLTs compared to the native lungs in SLTs. Airway metabolome distinguishes the allografts from native lungs and is associated with distinct microbial communities, suggesting a functional relationship between the local microbiome and metabolome.

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Section: Discussionmentioning

confidence: 82%

“…Next, we measured the levels of Ac-PGP, a collagen breakdown matrikine peptide that is known to upregulate neutrophil chemotaxis and increase lung vascular permeability [35,36]. We found that Ac-PGP was elevated (p = 0.03) in the allograft as compared to native lungs (Fig.…”

Section: Differences Between the Allograft And Native Lung Microbiomementioning

confidence: 90%

Differences in airway microbiome and metabolome of single lung transplant recipients

et al. 2020

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“…NET presence was found to be elevated in acute respiratory distress syndrome (ARDS) patients with ventilator-associated pneumonia compared to ARDS alone, and correlated with both bacterial burden and CXCL8 [81]. Considering that MPO has been found to be elevated in the airways of ARDS patients [82] and that this enzyme is associated with lung damage in CF [83,84], NET-associated MPO may be a contributing factor in progression of disease in ARDS. Studies of NETosis are also contributing to a better understanding of neutrophil plasticity.…”

Section: Bacterial Infectionsmentioning

confidence: 99%

Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

Giacalone

Margaroli

Mall

et al. 2020

IJMS

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Neutrophils have a prominent role in all human immune responses against any type of pathogen or stimulus. The lungs are a major neutrophil reservoir and neutrophilic inflammation is a primary response to both infectious and non-infectious challenges. While neutrophils are well known for their essential role in clearance of bacteria, they are also equipped with specific mechanisms to counter viruses and fungi. When these defense mechanisms become aberrantly activated in the absence of infection, this commonly results in debilitating chronic lung inflammation. Clearance of bacteria by phagocytosis is the hallmark role of neutrophils and has been studied extensively. New studies on neutrophil biology have revealed that this leukocyte subset is highly adaptable and fulfills diverse roles. Of special interest is how these adaptations can impact the outcome of an immune response in the lungs due to their potent capacity for clearing infection and causing damage to host tissue. The adaptability of neutrophils and their propensity to influence the outcome of immune responses implicates them as a much-needed target of future immunomodulatory therapies. This review highlights the recent advances elucidating the mechanisms of neutrophilic inflammation, with a focus on the lung environment due to the immense and growing public health burden of chronic lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), and acute lung inflammatory diseases such as transfusion-related acute lung injury (TRALI).

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“…Recent scientific reports provide information on the role of glyprolines in chronic inflammation. N‐acetylated PGP participates in the immune response as a neutrophil chemoattractant in lung diseases (COPD and cystic fibrosis), IBD, ischemic brain stroke as well as chorioamnionitis. Apart from proinflammatory activity, numerous beneficial effects of proline‐containing short sequences were observed.…”

Section: Biological Activity Of the Collagen‐derived Glyprolinesmentioning

confidence: 99%

“…Some of the airway disorders may be accompanied by impaired endothelial cell integrity. PGP has been shown to participate in the deregulation of vascular permeability as a result of activation of CXCR2 receptors on endothelial cells. Both local and systemic administration of PGP led to increased vascular leakage of pulmonary vessels similar to that caused by lipopolysaccharide present in the cell membrane of Gram‐negative bacteria strains.…”

Section: Biological Activity Of the Collagen‐derived Glyprolinesmentioning

confidence: 99%

Proline‐containing peptides—New insight and implications: A Review

Misiura

Miltyk

2019

BioFactors

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The family of regulatory proline‐containing peptides (PCPs), also known as glyprolines, exhibit significant biological activity. The group of glyprolines includes Gly‐Pro (GP), Pro‐Gly‐Pro (PGP), cyclic Gly‐Pro (cGP), as well as PGP derivatives, for example, N‐acetylated PGP (N‐a‐PGP) and N‐methylated PGP (N‐m‐PGP). PCPs are engaged in various biological processes including the proinflammatory neutrophil chemoattraction in lung diseases, inflammatory bowel diseases or ischemic stroke. Glyprolines have been also postulated to play an important role as atheroprotective and anticoagulant agents, exhibit neuroprotective effects in Parkinson's disease, as well as regulate insulin‐like growth factor (IGF) homeostasis. It was also noticed that PCPs inhibit proliferation and migration of keratinocytes in wound healing, protection of the gastric mucosa and stimulation of its regeneration. The regulatory glyprolines are derived from endogenous and exogenous sources. Most PCPs are derived from collagen or diet protein degradation. Recently, great interest is concentrated on short proline‐rich oligopeptides derived from IGF‐1 degradation. The mechanism of PCPs biological activity is not fully explained. It involves receptor‐mediated mechanisms, for example, N‐a‐PGP acts as CXCR1/2 receptor ligand, whereas cGP regulates IGF‐1 bioavailability by modifying the IGF‐1 binding to the IGF‐1 binding protein‐3. PGP has been observed to interact with collagen‐specific receptors. The data suggest a promising role of PGP as a target of various diseases therapy. This review is focused on the effect of PCPs on metabolic processes in different tissues and the molecular mechanism of their action as an approach to pharmacotherapy of PCPs‐dependent diseases.

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The neutrophil chemoattractant peptide proline-glycine-proline is associated with acute respiratory distress syndrome

Cited by 22 publications

References 52 publications

Differences in airway microbiome and metabolome of single lung transplant recipients

Differences in airway microbiome and metabolome of single lung transplant recipients

Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

Proline‐containing peptides—New insight and implications: A Review

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