• Am. J. Respir. Crit. Care Med. · Oct 2022

    Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension.

    • Shalina Taylor, Sarasa Isobe, Aiqin Cao, Kévin Contrepois, Bérénice A Benayoun, Lihua Jiang, Lingli Wang, Stavros Melemenidis, Mehmet O Ozen, Shoichiro Otsuki, Tsutomu Shinohara, Andrew J Sweatt, Jordan Kaplan, Jan-Renier Moonen, David P Marciano, Mingxia Gu, Kazuya Miyagawa, Brandon Hayes, Raymond G Sierra, Christopher J Kupitz, Patricia A Del Rosario, Andrew Hsi, ThompsonA A RogerAAR0000-0002-0717-4551Vera Moulton Wall Center for Pulmonary Vascular Diseases.Stanford Cardiovascular Institute.Department of Pediatrics - Cardiology.Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, , Maria E Ariza, Utkan Demirci, Roham T Zamanian, Francois Haddad, Mark R Nicolls, Michael P Snyder, and Marlene Rabinovitch.
    • Vera Moulton Wall Center for Pulmonary Vascular Diseases.
    • Am. J. Respir. Crit. Care Med. 2022 Oct 15; 206 (8): 101910341019-1034.

    AbstractRationale: The role of neutrophils and their extracellular vesicles (EVs) in the pathogenesis of pulmonary arterial hypertension is unclear. Objectives: To relate functional abnormalities in pulmonary arterial hypertension neutrophils and their EVs to mechanisms uncovered by proteomic and transcriptomic profiling. Methods: Production of elastase, release of extracellular traps, adhesion, and migration were assessed in neutrophils from patients with pulmonary arterial hypertension and control subjects. Proteomic analyses were applied to explain functional perturbations, and transcriptomic data were used to find underlying mechanisms. CD66b-specific neutrophil EVs were isolated from plasma of patients with pulmonary arterial hypertension, and we determined whether they produce pulmonary hypertension in mice. Measurements and Main Results: Neutrophils from patients with pulmonary arterial hypertension produce and release increased neutrophil elastase, associated with enhanced extracellular traps. They exhibit reduced migration and increased adhesion attributed to elevated β1-integrin and vinculin identified by proteomic analysis and previously linked to an antiviral response. This was substantiated by a transcriptomic IFN signature that we related to an increase in human endogenous retrovirus K envelope protein. Transfection of human endogenous retrovirus K envelope in a neutrophil cell line (HL-60) increases neutrophil elastase and IFN genes, whereas vinculin is increased by human endogenous retrovirus K deoxyuridine triphosphate diphosphatase that is elevated in patient plasma. Neutrophil EVs from patient plasma contain increased neutrophil elastase and human endogenous retrovirus K envelope and induce pulmonary hypertension in mice, mitigated by elafin, an elastase inhibitor. Conclusions: Elevated human endogenous retroviral elements and elastase link a neutrophil innate immune response to pulmonary arterial hypertension.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…

What will the 'Medical Journal of You' look like?

Start your free 21 day trial now.

We guarantee your privacy. Your email address will not be shared.