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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Korobkin, Julia-Jessica D. Deordieva, Ekaterina A. Tesakov, Ivan P. Adamanskaya, Ekaterina-Iva A. Boldova, Anna E. Boldyreva, Antonina A. Galkina, Sofia V. Lazutova, Daria P. Martyanov, Alexey A. Pustovalov, Vitaly A. Novichkova, Galina A. Shcherbina, Anna Panteleev, Mikhail A. Sveshnikova, Anastasia N. |
| Abstract | 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 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 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 In samples from healthy donors, but not SDS patients, neutrophils move in the direction of large, chemoattractant-releasing platelet thrombi growing on collagen. |
| Related Links | https://bmcbiol.biomedcentral.com/counter/pdf/10.1186/s12915-024-01912-2.pdf |
| Ending Page | 17 |
| Page Count | 17 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17417007 |
| DOI | 10.1186/s12915-024-01912-2 |
| Journal | BMC Biology |
| Issue Number | 1 |
| Volume Number | 22 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-05-20 |
| Access Restriction | Open |
| Subject Keyword | Life Sciences Chemotaxis Hemostasis Neutrophils Platelets Thromboinflammation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Ecology, Evolution, Behavior and Systematics Structural Biology Biochemistry, Genetics and Molecular Biology Plant Science Biotechnology Physiology Agricultural and Biological Sciences Cell Biology Developmental Biology |
| Journal Impact Factor | 4.4/2023 |
| 5-Year Journal Impact Factor | 5.4/2023 |
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