Dissecting thrombus-directed chemotaxis and random movement in neutrophil near-thrombus motion in flow chambers.


Journal

BMC biology
ISSN: 1741-7007
Titre abrégé: BMC Biol
Pays: England
ID NLM: 101190720

Informations de publication

Date de publication:
20 May 2024
Historique:
received: 23 11 2023
accepted: 08 05 2024
medline: 20 5 2024
pubmed: 20 5 2024
entrez: 19 5 2024
Statut: epublish

Résumé

Thromboinflammation is caused by mutual activation of platelets and neutrophils. The site of thromboinflammation is determined by chemoattracting agents release by endothelium, immune cells, and platelets. Impaired neutrophil chemotaxis contributes to the pathogenesis of Shwachman-Diamond syndrome (SDS). In this hereditary disorder, neutrophils are known to have aberrant chemoattractant-induced F-actin properties. Here, we aim to determine whether neutrophil chemotaxis could be analyzed using our previously developed ex vivo assay of the neutrophils crawling among the growing thrombi. Adult and pediatric healthy donors, alongside with pediatric patients with SDS, were recruited for the study. Thrombus formation and granulocyte movement in hirudinated whole blood were visualized by fluorescent microscopy in fibrillar collagen-coated parallel-plate flow chambers. Alternatively, fibrinogen, fibronectin, vWF, or single tumor cells immobilized on coverslips were used. A computational model of chemokine distribution in flow chamber with a virtual neutrophil moving in it was used to analyze the observed data. The movement of healthy donor neutrophils predominantly occurred in the direction and vicinity of thrombi grown on collagen or around tumor cells. For SDS patients or on coatings other than collagen, the movement was characterized by randomness and significantly reduced velocities. Increase in wall shear rates to 300-500 1/s led to an increase in the proportion of rolling neutrophils. A stochastic algorithm simulating leucocyte chemotaxis movement in the calculated chemoattractant field could reproduce the experimental trajectories of moving neutrophils for 72% of cells. In samples from healthy donors, but not SDS patients, neutrophils move in the direction of large, chemoattractant-releasing platelet thrombi growing on collagen.

Sections du résumé

BACKGROUND BACKGROUND
Thromboinflammation is caused by mutual activation of platelets and neutrophils. The site of thromboinflammation is determined by chemoattracting agents release by endothelium, immune cells, and platelets. Impaired neutrophil chemotaxis contributes to the pathogenesis of Shwachman-Diamond syndrome (SDS). In this hereditary disorder, neutrophils are known to have aberrant chemoattractant-induced F-actin properties. Here, we aim to determine whether neutrophil chemotaxis could be analyzed using our previously developed ex vivo assay of the neutrophils crawling among the growing thrombi.
METHODS METHODS
Adult and pediatric healthy donors, alongside with pediatric patients with SDS, were recruited for the study. Thrombus formation and granulocyte movement in hirudinated whole blood were visualized by fluorescent microscopy in fibrillar collagen-coated parallel-plate flow chambers. Alternatively, fibrinogen, fibronectin, vWF, or single tumor cells immobilized on coverslips were used. A computational model of chemokine distribution in flow chamber with a virtual neutrophil moving in it was used to analyze the observed data.
RESULTS RESULTS
The movement of healthy donor neutrophils predominantly occurred in the direction and vicinity of thrombi grown on collagen or around tumor cells. For SDS patients or on coatings other than collagen, the movement was characterized by randomness and significantly reduced velocities. Increase in wall shear rates to 300-500 1/s led to an increase in the proportion of rolling neutrophils. A stochastic algorithm simulating leucocyte chemotaxis movement in the calculated chemoattractant field could reproduce the experimental trajectories of moving neutrophils for 72% of cells.
CONCLUSIONS CONCLUSIONS
In samples from healthy donors, but not SDS patients, neutrophils move in the direction of large, chemoattractant-releasing platelet thrombi growing on collagen.

Identifiants

pubmed: 38764040
doi: 10.1186/s12915-024-01912-2
pii: 10.1186/s12915-024-01912-2
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

115

Subventions

Organisme : Russian Science Foundation
ID : 23-45-10039

Informations de copyright

© 2024. The Author(s).

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Auteurs

Julia-Jessica D Korobkin (JD)

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.

Ekaterina A Deordieva (EA)

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Ivan P Tesakov (IP)

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Department of Oncology, Hematology, Immunology, and Rheumatology, University Hospital Tübingen, Tübingen, Germany.

Ekaterina-Iva A Adamanskaya (EA)

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Anna E Boldova (AE)

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Antonina A Boldyreva (AA)

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.
Sechenov First Moscow State Medical University, Moscow, Russia.

Sofia V Galkina (SV)

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Daria P Lazutova (DP)

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.

Alexey A Martyanov (AA)

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.

Vitaly A Pustovalov (VA)

Federal Institute of Technology Zurich, Zurich, Switzerland.

Galina A Novichkova (GA)

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Anna Shcherbina (A)

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Mikhail A Panteleev (MA)

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Lomonosov Moscow State University, Moscow, Russia.

Anastasia N Sveshnikova (AN)

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia. a.sveshnikova@physics.msu.ru.
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. a.sveshnikova@physics.msu.ru.
Lomonosov Moscow State University, Moscow, Russia. a.sveshnikova@physics.msu.ru.

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