ArticleBlood2021
Placental HTRA1 cleaves α1-antitrypsin to generate a NET-inhibitory peptide.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- A 'Tangled Web' in the CNS: unraveling neutrophil extracellular traps in neurological disorders.Molecular neurodegeneration · 2026Review
- Protein Fragments: From Biomarkers to Therapeutic Targets-A Focus on α1-Antitrypsin-Derived Peptides.Mediators of inflammation · 2026Review
- NETosis-specific cell death: a novel mechanism in the pathogenesis of gouty arthritis.European journal of medical research · 2025Review
- Genome-wide association analyses identify distinct genetic architectures for age-related macular degeneration across ancestries.Nature genetics · 2024Article
- Neonatal NET-inhibitory factor inhibits macrophage extracellular trap formation.Blood advances · 2024Article
- A promising frontier: targeting NETs for stroke treatment breakthroughs.Cell communication and signaling : CCS · 2024Review
- Platelets in Alcohol-Associated Liver Disease: Interaction With Neutrophils.Cellular and molecular gastroenterology and hepatology · 2024Review
- Alpha-1-antitrypsin as novel substrate forFrontiers in immunology · 2024Article
- Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity.The American journal of pathology · 2023Article
- An anoikis-based gene signature for predicting prognosis in malignant pleural mesothelioma and revealing immune infiltration.Journal of cancer research and clinical oncology · 2023Article
- Neutrophil extracellular trap inhibition improves survival in neonatal mouse infectious peritonitis.Pediatric research · 2023Article
- Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants.Children (Basel, Switzerland) · 2022Article
- Neutrophil extracellular traps regulate ischemic stroke brain injury.The Journal of clinical investigation · 2022Article
- Investigating the Link between Alpha-1 Antitrypsin and Human Neutrophil Elastase in Bronchoalveolar Lavage Fluid of COVID-19 Patients.Current issues in molecular biology · 2022Article
- Multiplex quantification of C-terminal alpha-1-antitrypsin peptides provides a novel approach for characterizing systemic inflammation.Scientific reports · 2022Article
- Neonatal NET-Inhibitory Factor improves survival in the cecal ligation and puncture model of polymicrobial sepsis by inhibiting neutrophil extracellular traps.Frontiers in immunology · 2022Article
- The role of extracellular traps in ischemia reperfusion injury.Frontiers in immunology · 2022Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Neutrophil extracellular traps (NETs) are important components of innate immunity. Neonatal neutrophils (polymorphonuclear leukocytes [PMNs]) fail to form NETs due to circulating NET-inhibitory peptides (NIPs), cleavage fragments of α1-antitrypsin (A1AT). How fetal and neonatal blood NIPs are generated remains unknown, however. The placenta expresses high-temperature requirement serine protease A1 (HTRA1) during fetal development, which can cleave A1AT. We hypothesized that placentally expressed HTRA1 regulates the formation of NIPs and that NET competency changed in PMNs isolated from neonatal HTRA1 knockout mice (HTRA1-/-). We found that umbilical cord blood plasma has elevated HTRA1 levels compared with adult plasma and that recombinant and placenta-eluted HTRA1 cleaves A1AT to generate an A1AT cleavage fragment (A1ATM383S-CF) of molecular weight similar to previously identified NIPs that block NET formation by adult neutrophils. We showed that neonatal mouse pup plasma contains A1AT fragments that inhibit NET formation by PMNs isolated from adult mice, indicating that NIP generation during gestation is conserved across species. Lipopolysaccharide-stimulated PMNs isolated from HTRA1+/+ littermate control pups exhibit delayed NET formation after birth. However, plasma from HTRA1-/- pups had no detectable NIPs, and PMNs from HTRA1-/- pups became NET competent earlier after birth compared with HTRA1+/+ littermate controls. Finally, in the cecal slurry model of neonatal sepsis, A1ATM383S-CF improved survival in C57BL/6 pups by preventing pathogenic NET formation. Our data indicate that placentally expressed HTRA1 is a serine protease that cleaves A1AT in utero to generate NIPs that regulate NET formation by human and mouse PMNs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.