학술논문
Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation.
Document Type
Academic Journal
Author
Zhao G; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. zhaogan@vet.upenn.edu.; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. zhaogan@vet.upenn.edu.; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA. zhaogan@vet.upenn.edu.; Gentile ME; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Xue L; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Cosgriff CV; Pulmonary and Critical Care Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.; Weiner AI; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Adams-Tzivelekidis S; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Wong J; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Li X; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Kass-Gergi S; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Holcomb NP; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Basal MC; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Stewart KM; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Planer JD; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Cantu E; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Division of Cardiovascular Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Christie JD; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Crespo MM; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Mitchell MJ; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Meyer NJ; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Vaughan AE; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. andrewva@vet.upenn.edu.; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. andrewva@vet.upenn.edu.; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA. andrewva@vet.upenn.edu.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
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.
(© 2024. The Author(s).)
(© 2024. The Author(s).)