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Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019.
Metzemaekers, Mieke; Cambier, Seppe; Blanter, Marfa; Vandooren, Jennifer; de Carvalho, Ana Carolina; Malengier-Devlies, Bert; Vanderbeke, Lore; Jacobs, Cato; Coenen, Sofie; Martens, Erik; Pörtner, Noëmie; Vanbrabant, Lotte; Van Mol, Pierre; Van Herck, Yannick; Van Aerde, Nathalie; Hermans, Greet; Gunst, Jan; Borin, Alexandre; Toledo N Pereira, Bruna; Dos Sp Gomes, Arilson Bernardo; Primon Muraro, Stéfanie; Fabiano de Souza, Gabriela; S Farias, Alessandro; Proenca-Modena, José Luiz; R Vinolo, Marco Aurélio; Marques, Pedro Elias; Wouters, Carine; Wauters, Els; Struyf, Sofie; Matthys, Patrick; Opdenakker, Ghislain; Marques, Rafael Elias; Wauters, Joost; Gouwy, Mieke; Proost, Paul.
  • Metzemaekers M; Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • Cambier S; Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • Blanter M; Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • Vandooren J; Laboratory of Immunobiology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • de Carvalho AC; Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • Malengier-Devlies B; Brazilian Center for Research in Energy and Materials - CNPEM Brazilian Biosciences National Laboratory Campinas LNBio Brazil.
  • Vanderbeke L; Laboratory of Immunoinflammation Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil.
  • Jacobs C; Laboratory of Immunobiology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • Coenen S; Laboratory of Clinical Bacteriology and Mycology Department of Microbiology, Immunology and Transplantation KU Leuven Leuven Belgium.
  • Martens E; Laboratory for Clinical Infectious and Inflammatory Disorders Department of Microbiology, Immunology and Transplantation KU Leuven Leuven Belgium.
  • Pörtner N; Division of Pediatrics University Hospitals Leuven Leuven Belgium.
  • Vanbrabant L; Laboratory of Immunobiology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • Van Mol P; Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • Van Herck Y; Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • Van Aerde N; Laboratory of Translational Genetics Department of Human Genetics VIB-KU Leuven Leuven Belgium.
  • Hermans G; Laboratory of Experimental Oncology Department of Oncology KU Leuven Leuven Belgium.
  • Gunst J; Laboratory of Intensive Care Medicine Department of Cellular and Molecular Medicine KU Leuven Leuven Belgium.
  • Borin A; Laboratory of Intensive Care Medicine Department of Cellular and Molecular Medicine KU Leuven Leuven Belgium.
  • Toledo N Pereira B; Laboratory of Intensive Care Medicine Department of Cellular and Molecular Medicine KU Leuven Leuven Belgium.
  • Dos Sp Gomes AB; Brazilian Center for Research in Energy and Materials - CNPEM Brazilian Biosciences National Laboratory Campinas LNBio Brazil.
  • Primon Muraro S; Laboratory of Immunoinflammation Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil.
  • Fabiano de Souza G; Laboratory of Immunoinflammation Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil.
  • S Farias A; Laboratory Emerging Viruses Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil.
  • Proenca-Modena JL; Laboratory Emerging Viruses Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil.
  • R Vinolo MA; Experimental Medicine Research Cluster (EMRC) University of Campinas (UNICAMP) Campinas Brazil.
  • Marques PE; Experimental Medicine Research Cluster (EMRC) University of Campinas (UNICAMP) Campinas Brazil.
  • Wouters C; Laboratory of Immunoinflammation Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil.
  • Wauters E; Experimental Medicine Research Cluster (EMRC) University of Campinas (UNICAMP) Campinas Brazil.
  • Matthys P; Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • Opdenakker G; Laboratory of Immunobiology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
  • Marques RE; Division of Pediatric Rheumatology University Hospitals Leuven Leuven Belgium.
  • Wauters J; European Reference Network for Rare Immunodeficiency Autoinflammatory and Autoimmune Diseases (RITA) at University Hospitals Leuven Leuven Belgium.
  • Gouwy M; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE) Department of Chronic Diseases and Metabolism KU Leuven Leuven Belgium.
  • Proost P; Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium.
Clin Transl Immunology ; 10(4): e1271, 2021.
Article in English | MEDLINE | ID: covidwho-1525427
Semantic information from SemMedBD (by NLM)
1. Evaluation procedure TREATS COVID-19
Subject
Evaluation procedure
Predicate
TREATS
Object
COVID-19
2. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
3. Blood PART_OF Patients
Subject
Blood
Predicate
PART_OF
Object
Patients
4. Kinetics AFFECTS Neutrophil migratio
Subject
Kinetics
Predicate
AFFECTS
Object
Neutrophil migratio
5. Plasma LOCATION_OF Peptide Hydrolases
Subject
Plasma
Predicate
LOCATION_OF
Object
Peptide Hydrolases
6. Plasma LOCATION_OF cytokine
Subject
Plasma
Predicate
LOCATION_OF
Object
cytokine
7. Plasma LOCATION_OF chemokine
Subject
Plasma
Predicate
LOCATION_OF
Object
chemokine
8. neutrophil LOCATION_OF Virus Replication
Subject
neutrophil
Predicate
LOCATION_OF
Object
Virus Replication
9. Human Neprilysin|MME INHIBITS CXCR2 gene|CXCR2
Subject
Human Neprilysin|MME
Predicate
INHIBITS
Object
CXCR2 gene|CXCR2
10. Human Neprilysin|MME INHIBITS C5AR1 gene|C5AR1
Subject
Human Neprilysin|MME
Predicate
INHIBITS
Object
C5AR1 gene|C5AR1
11. Patients LOCATION_OF Plasma
Subject
Patients
Predicate
LOCATION_OF
Object
Plasma
12. Plasma LOCATION_OF Leukocyte Elastase
Subject
Plasma
Predicate
LOCATION_OF
Object
Leukocyte Elastase
13. High Level PROCESS_OF Patients
Subject
High Level
Predicate
PROCESS_OF
Object
Patients
14. CXCL8 AFFECTS neutrophil
Subject
CXCL8
Predicate
AFFECTS
Object
neutrophil
15. CXCL12 gene|CXCL12 AFFECTS neutrophil
Subject
CXCL12 gene|CXCL12
Predicate
AFFECTS
Object
neutrophil
16. neutrophil PART_OF Homo sapiens
Subject
neutrophil
Predicate
PART_OF
Object
Homo sapiens
17. neutrophil NEG_LOCATION_OF 2019 novel coronavirus
Subject
neutrophil
Predicate
NEG_LOCATION_OF
Object
2019 novel coronavirus
18. physiological aspects PROCESS_OF Patients
Subject
physiological aspects
Predicate
PROCESS_OF
Object
Patients
19. physiological aspects COEXISTS_WITH Circulatory Process
Subject
physiological aspects
Predicate
COEXISTS_WITH
Object
Circulatory Process
20. Evaluation procedure TREATS COVID-19
Subject
Evaluation procedure
Predicate
TREATS
Object
COVID-19
21. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
22. Blood PART_OF Patients
Subject
Blood
Predicate
PART_OF
Object
Patients
23. Kinetics AFFECTS Neutrophil migration, function
Subject
Kinetics
Predicate
AFFECTS
Object
Neutrophil migration, function
24. Plasma LOCATION_OF Peptide Hydrolases
Subject
Plasma
Predicate
LOCATION_OF
Object
Peptide Hydrolases
25. Plasma LOCATION_OF cytokine
Subject
Plasma
Predicate
LOCATION_OF
Object
cytokine
26. Plasma LOCATION_OF chemokine
Subject
Plasma
Predicate
LOCATION_OF
Object
chemokine
27. neutrophil LOCATION_OF Virus Replication
Subject
neutrophil
Predicate
LOCATION_OF
Object
Virus Replication
28. Human Neprilysin|MME INHIBITS CXCR2 gene|CXCR2
Subject
Human Neprilysin|MME
Predicate
INHIBITS
Object
CXCR2 gene|CXCR2
29. Human Neprilysin|MME INHIBITS C5AR1 gene|C5AR1
Subject
Human Neprilysin|MME
Predicate
INHIBITS
Object
C5AR1 gene|C5AR1
30. Patients LOCATION_OF Plasma
Subject
Patients
Predicate
LOCATION_OF
Object
Plasma
31. Plasma LOCATION_OF Leukocyte Elastase
Subject
Plasma
Predicate
LOCATION_OF
Object
Leukocyte Elastase
32. High Level PROCESS_OF Patients
Subject
High Level
Predicate
PROCESS_OF
Object
Patients
33. CXCL8 AFFECTS neutrophil
Subject
CXCL8
Predicate
AFFECTS
Object
neutrophil
34. CXCL12 gene|CXCL12 AFFECTS neutrophil
Subject
CXCL12 gene|CXCL12
Predicate
AFFECTS
Object
neutrophil
35. neutrophil PART_OF Homo sapiens
Subject
neutrophil
Predicate
PART_OF
Object
Homo sapiens
36. neutrophil NEG_LOCATION_OF 2019 novel coronavirus
Subject
neutrophil
Predicate
NEG_LOCATION_OF
Object
2019 novel coronavirus
37. physiological aspects PROCESS_OF Patients
Subject
physiological aspects
Predicate
PROCESS_OF
Object
Patients
38. physiological aspects COEXISTS_WITH Circulatory Process
Subject
physiological aspects
Predicate
COEXISTS_WITH
Object
Circulatory Process
ABSTRACT

OBJECTIVES:

Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID-19). We isolated neutrophils from the blood of COVID-19 patients receiving general ward care and from patients hospitalised at intensive care units (ICUs) to explore the kinetics of circulating neutrophils and factors important for neutrophil migration and activation.

METHODS:

Multicolour flow cytometry was exploited for the analysis of neutrophil differentiation and activation markers. Multiplex and ELISA technologies were used for the quantification of protease, protease inhibitor, chemokine and cytokine concentrations in plasma. Neutrophil polarisation responses were evaluated microscopically. Gelatinolytic and metalloproteinase activity in plasma was determined using a fluorogenic substrate. Co-culturing healthy donor neutrophils with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) allowed us to investigate viral replication in neutrophils.

RESULTS:

Upon ICU admission, patients displayed high plasma concentrations of granulocyte-colony-stimulating factor (G-CSF) and the chemokine CXCL8, accompanied by emergency myelopoiesis as illustrated by high levels of circulating CD10-, immature neutrophils with reduced CXCR2 and C5aR expression. Neutrophil elastase and non-metalloproteinase-derived gelatinolytic activity were increased in plasma from ICU patients. Significantly higher levels of circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) in patients at ICU admission yielded decreased total MMP proteolytic activity in blood. COVID-19 neutrophils were hyper-responsive to CXCL8 and CXCL12 in shape change assays. Finally, SARS-CoV-2 failed to replicate inside human neutrophils.

CONCLUSION:

Our study provides detailed insights into the kinetics of neutrophil phenotype and function in severe COVID-19 patients, and supports the concept of an increased neutrophil activation state in the circulation.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Language: English Journal: Clin Transl Immunology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Language: English Journal: Clin Transl Immunology Year: 2021 Document Type: Article