Red blood cell-derived semaphorin 7A promotes thrombo-inflammation in myocardial ischemia-reperfusion injury through platelet GPIb

Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet–neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here,...

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Veröffentlicht in:Nature communications Jg. 11; H. 1; S. 1315 - 12
Hauptverfasser: Köhler, David, Granja, Tiago, Volz, Julia, Koeppen, Michael, Langer, Harald F., Hansmann, Georg, Legchenko, Ekaterina, Geisler, Tobias, Bakchoul, Tamam, Eggstein, Claudia, Häberle, Helene A., Nieswandt, Bernhard, Rosenberger, Peter
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 11.03.2020
Nature Publishing Group
Nature Portfolio
Schlagworte:
13/1
13/31
14/63
59/36
59/5
64/60
692/4019/592/1339
692/4019/592/75/2/1674
692/420/256/2516
82/51
82/80
96/106
96/2
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Antibodies
Antigens, CD - genetics
Antigens, CD - immunology
Antigens, CD - metabolism
Axon guidance
Blood platelets
Blood Platelets - immunology
Blood Platelets - metabolism
Complex formation
Coronary Vessels - pathology
Disease Models, Animal
Erythrocytes
Erythrocytes - immunology
Erythrocytes - metabolism
Female
Genetic modification
Glycoproteins
GPI-Linked Proteins - genetics
GPI-Linked Proteins - immunology
GPI-Linked Proteins - metabolism
Health problems
Humanities and Social Sciences
Humans
Inflammation
Injuries
Ischemia
Male
Mice
Mice, Knockout
Middle Aged
multidisciplinary
Myocardial infarction
Myocardial Infarction - blood
Myocardial Infarction - immunology
Myocardial Infarction - pathology
Myocardial ischemia
Myocardial Reperfusion Injury - blood
Myocardial Reperfusion Injury - immunology
Myocardial Reperfusion Injury - pathology
Myocardium - pathology
Neutrophils
Perfusion
Platelet Glycoprotein GPIb-IX Complex - metabolism
Platelets
Prospective Studies
Reperfusion
Science
Science (multidisciplinary)
Semaphorins - genetics
Semaphorins - immunology
Semaphorins - metabolism
Thrombosis - immunology
Thrombosis - pathology
Young Adult
ISSN:2041-1723, 2041-1723
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Zusammenfassung:Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet–neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet–neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury. Reperfusion injury following myocardial ischemia is aggravated by inflammation and platelet–neutrophil complex formation. Here the authors show that semaphorin 7A binds to platelet GPIb, enhancing platelet–neutrophil interaction and increasing post-ischemic myocardial tissue injury, and that blockage of semaphorin 7A is protective.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-14958-x