Neutrophils mediate pulmonary artery thrombosis in situ

Olga Porembskaya, Vsevolod Zinserling, Vladimir Tomson, Yana Toropova, Eleonora Starikova, Vitaliy Maslei, Nika Bulavinova, Olga Kirik, Marina Syrtsova, Leonid Laberko, Maxim Galchenko, Vyacheslav Kravchuk, Sergey Saiganov, Alexander Brill

Research output: Contribution to journalArticlepeer-review

Abstract

Pulmonary embolism is a life-threatening condition, which can result in respiratory insufficiency and death. Blood clots occluding branches of the pulmonary artery (PA) are traditionally considered to originate from thrombi in deep veins (usually in legs). However, growing evidence suggests that occlusion of the vessels in the lungs can develop without preceding deep vein thrombosis (DVT). In this work, we used an inferior vena cava (IVC) complete ligation model of DVT in Wistar rats to explore the possibility and mechanisms of PA thrombosis under the conditions where all routes of thrombotic mass migration from peripheral veins are blocked. We demonstrate that rats both with normal and reduced neutrophil counts developed thrombi in the IVC, although, neutropenia caused a substantial decrease in thrombus size and a shift from fresh fibrin toward mature fibrin and connective tissue inside the thrombus. Massive fibrin deposition was found in the PA branches in the majority of DVT rats with normal neutrophil counts, but in none of the neutropenic animals. Neutrophil ablation also abolished macroscopic signs of lung damage. Altogether, the results demonstrate that thrombi in the lung vasculature can form in situ by mechanisms that require local neutrophil recruitment taking place in the DVT setting.
Original languageEnglish
Article number5829
Number of pages9
JournalInternational Journal of Molecular Sciences
Volume23
Issue number10
DOIs
Publication statusPublished - 23 May 2022

Keywords

  • deep vein thrombosis
  • pulmonary embolism
  • neutrophils

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