IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48589-3.html
   My bibliography  Save this article

Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation

Author

Listed:
  • Gan Zhao

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Maria E. Gentile

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Lulu Xue

    (University of Pennsylvania)

  • Christopher V. Cosgriff

    (Massachusetts General Hospital and Harvard Medical School)

  • Aaron I. Weiner

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Stephanie Adams-Tzivelekidis

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Joanna Wong

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Xinyuan Li

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Sara Kass-Gergi

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Nicolas P. Holcomb

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Maria C. Basal

    (University of Pennsylvania
    University of Pennsylvania)

  • Kathleen M. Stewart

    (University of Pennsylvania
    University of Pennsylvania)

  • Joseph D. Planer

    (University of Pennsylvania
    University of Pennsylvania)

  • Edward Cantu

    (University of Pennsylvania
    University of Pennsylvania)

  • Jason D. Christie

    (University of Pennsylvania
    University of Pennsylvania)

  • Maria M. Crespo

    (University of Pennsylvania
    University of Pennsylvania)

  • Michael J. Mitchell

    (University of Pennsylvania)

  • Nuala J. Meyer

    (University of Pennsylvania
    University of Pennsylvania)

  • Andrew E. Vaughan

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

Abstract

Inflammation induced by lung infection is a double-edged sword, moderating both anti-viral and immune pathogenesis effects; the mechanism of the latter is not fully understood. Previous studies suggest the vasculature is involved in tissue injury. Here, we report that expression of Sparcl1, a secreted matricellular protein, is upregulated in pulmonary capillary endothelial cells (EC) during influenza-induced lung injury. Endothelial overexpression of SPARCL1 promotes detrimental lung inflammation, with SPARCL1 inducing ‘M1-like’ macrophages and related pro-inflammatory cytokines, while SPARCL1 deletion alleviates these effects. Mechanistically, SPARCL1 functions through TLR4 on macrophages in vitro, while TLR4 inhibition in vivo ameliorates excessive inflammation caused by endothelial Sparcl1 overexpression. Finally, SPARCL1 expression is increased in lung ECs from COVID-19 patients when compared with healthy donors, while fatal COVID-19 correlates with higher circulating SPARCL1 protein levels in the plasma. Our results thus implicate SPARCL1 as a potential prognosis biomarker for deadly COVID-19 pneumonia and as a therapeutic target for taming hyperinflammation in pneumonia.

Suggested Citation

  • Gan Zhao & Maria E. Gentile & Lulu Xue & Christopher V. Cosgriff & Aaron I. Weiner & Stephanie Adams-Tzivelekidis & Joanna Wong & Xinyuan Li & Sara Kass-Gergi & Nicolas P. Holcomb & Maria C. Basal & K, 2024. "Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48589-3
    DOI: 10.1038/s41467-024-48589-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48589-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-48589-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Joey Schyns & Qiang Bai & Cecilia Ruscitti & Coraline Radermecker & Sebastiaan Schepper & Svetoslav Chakarov & Frédéric Farnir & Dimitri Pirottin & Florent Ginhoux & Guy Boeckxstaens & Fabrice Bureau , 2019. "Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    2. Astrid Gillich & Fan Zhang & Colleen G. Farmer & Kyle J. Travaglini & Serena Y. Tan & Mingxia Gu & Bin Zhou & Jeffrey A. Feinstein & Mark A. Krasnow & Ross J. Metzger, 2020. "Capillary cell-type specialization in the alveolus," Nature, Nature, vol. 586(7831), pages 785-789, October.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ahmed A. Raslan & Tho X. Pham & Jisu Lee & Konstantinos Kontodimas & Andrew Tilston-Lunel & Jillian Schmottlach & Jeongmin Hong & Taha Dinc & Andreea M. Bujor & Nunzia Caporarello & Aude Thiriot & Ulr, 2024. "Lung injury-induced activated endothelial cell states persist in aging-associated progressive fibrosis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Hongryeol Park & Jian Song & Hyun-Woo Jeong & Max L. B. Grönloh & Bong Ihn Koh & Esther Bovay & Kee-Pyo Kim & Luisa Klotz & Patricia A. Thistlethwaite & Jaap D. Buul & Lydia Sorokin & Ralf H. Adams, 2024. "Apelin modulates inflammation and leukocyte recruitment in experimental autoimmune encephalomyelitis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Nunzia Caporarello & Jisu Lee & Tho X. Pham & Dakota L. Jones & Jiazhen Guan & Patrick A. Link & Jeffrey A. Meridew & Grace Marden & Takashi Yamashita & Collin A. Osborne & Aditya V. Bhagwate & Steven, 2022. "Dysfunctional ERG signaling drives pulmonary vascular aging and persistent fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Ning Yang & Joseph M. Luna & Peihong Dai & Yi Wang & Charles M. Rice & Liang Deng, 2022. "Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Sarasa Isobe & Ramesh V. Nair & Helen Y. Kang & Lingli Wang & Jan-Renier Moonen & Tsutomu Shinohara & Aiqin Cao & Shalina Taylor & Shoichiro Otsuki & David P. Marciano & Rebecca L. Harper & Mir S. Adi, 2023. "Reduced FOXF1 links unrepaired DNA damage to pulmonary arterial hypertension," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Guolun Wang & Bingqiang Wen & Minzhe Guo & Enhong Li & Yufang Zhang & Jeffrey A. Whitsett & Tanya V. Kalin & Vladimir V. Kalinichenko, 2024. "Identification of endothelial and mesenchymal FOXF1 enhancers involved in alveolar capillary dysplasia," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Amit A. Upadhyay & Elise G. Viox & Timothy N. Hoang & Arun K. Boddapati & Maria Pino & Michelle Y.-H. Lee & Jacqueline Corry & Zachary Strongin & David A. Cowan & Elizabeth N. Beagle & Tristan R. Hort, 2023. "TREM2+ and interstitial-like macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Guolun Wang & Bingqiang Wen & Zicheng Deng & Yufang Zhang & Olena A. Kolesnichenko & Vladimir Ustiyan & Arun Pradhan & Tanya V. Kalin & Vladimir V. Kalinichenko, 2022. "Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48589-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.