| First Author | Yuan Y | Year | 2017 |
| Journal | Sci Transl Med | Volume | 9 |
| Issue | 409 | PubMed ID | 28954929 |
| Mgi Jnum | J:248473 | Mgi Id | MGI:5917056 |
| Doi | 10.1126/scitranslmed.aam5861 | Citation | Yuan Y, et al. (2017) Neutrophil macroaggregates promote widespread pulmonary thrombosis after gut ischemia. Sci Transl Med 9(409) |
| abstractText | Gut ischemia is common in critically ill patients, promoting thrombosis and inflammation in distant organs. The mechanisms linking hemodynamic changes in the gut to remote organ thrombosis remain ill-defined. We demonstrate that gut ischemia in the mouse induces a distinct pulmonary thrombotic disorder triggered by neutrophil macroaggregates. These neutrophil aggregates lead to widespread occlusion of pulmonary arteries, veins, and the microvasculature. A similar pulmonary neutrophil-rich thrombotic response occurred in humans with the acute respiratory distress syndrome. Intravital microscopy during gut ischemia-reperfusion injury revealed that rolling neutrophils extract large membrane fragments from remnant dying platelets in multiple organs. These platelet fragments bridge adjacent neutrophils to facilitate macroaggregation. Platelet-specific deletion of cyclophilin D, a mitochondrial regulator of cell necrosis, prevented neutrophil macroaggregation and pulmonary thrombosis. Our studies demonstrate the existence of a distinct pulmonary thrombotic disorder triggered by dying platelets and neutrophil macroaggregates. Therapeutic targeting of platelet death pathways may reduce pulmonary thrombosis in critically ill patients. |
