Abstract Number: PB1843
Meeting: ISTH 2020 Congress
Background: Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive and irreversible disease leading to death between 2 to 5 years after diagnosis. Despite the significant morbidity and mortality associated with IPF, its pathogenesis remains poorly understood and there is no curative treatment. Recent evidence showed that platelets are in a preactivated state in blood of IPF patients. However, the role of platelets and activation mechanisms during the development of IPF have not been established yet.
Aims: To decipher the role of platelets during pulmonary fibrosis
Methods: We used intratracheal instillation of bleomycin to induce pulmonary fibrosis in mice and collected their bronchoalveolar lavages (BAL) fluids, blood and lungs. Mice treated with intratracheal saline were used as controls.
Results: Wild-Type (WT) mice display a significative higher mortality rate 14 days after bleomycin instillation compared to the control group. Platelets and white blood cells counts increase in BAL of bleomycin-treated mice. Interestingly, thrombocytopenic (TP) mice challenged with bleomycin died prematurely after instillation. To further identify platelet mechanisms involved, mice lacking the GPIbα subunit of the von Willebrand factor receptor (hIL4R/GPIbα) died prematurely 6 days after instillation. Remarkably, mice deficient for the collagen receptor, GPVI, are protected from mortality after bleomycin instillation. Hemoglobin level, in the BAL, was significantly higher in bleomycin-induced TP and hIL4R/GPIbα mice compared to bleomycin-induced GPVI deficient and WT mice. Moreover, platelet factor 4 level in BAL from GPVI deficient mice is significantly decreased compared to WT mice.
Conclusions: Here we showed that platelets play a protective role during pulmonary fibrosis. We uncovered that GPVI plays a deleterious role in pulmonary fibrosis and GPIbα is required for the maintenance of vascular integrity in bleomycin-treated mice. Our studies require further experiments to explore other platelet signaling molecules and highlight a new potential therapeutic target in IPF.
To cite this abstract in AMA style:Martos R, Machkour I, Chalghoumi R, Yahiaoui K, Lebas H, Bergemeier W, Nieswandt B, Arocas V, Bouton M-, Boulaftali Y. Critical Role of Platelets during Pulmonary Fibrosis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/critical-role-of-platelets-during-pulmonary-fibrosis/. Accessed August 15, 2022.
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