Abstract 156: Role of Platelets in Maintaining Hemostasis and Coagulation Activation in Viral-induced Acute Respiratory Distress Syndrome (ards) in Mice

Abstract

Platelets are crucial players during viral infections, as bridge hemostasis, inflammation, and immune response. RNA viruses like IAV are associated with pathologic platelet activation and thrombosis. We are currently investigating how platelet depletion before or post initial IAV infection can affect disease outcome. WT mice were infected with IAV (0.02HAU, intranasally) for 7 days to induce viral ARDS. Mice were injected with platelet depletion antibody R300 or control IgG at day 0 (prior) and day 3 (after infection). Mice treated with R300/control IgG were subjected to dsRNA mimetic poly IC intranasally for 3 days to induce virus-like ARDS. Global lung function was recorded, plasma and BALF were collected 7 or 3 dpi or final poly IC treatment, respectively. BALF cellularity and blood cellular composition was analyzed. Markers of lung injury and cytokines were measured. We observed that IAV infection leads to local lung inflammation, coagulation activation and ARDS-like lung dysfunction. Mice treated with R300 showed severe thrombocytopenia in blood. We observed more impaired alveolar hemostasis and increased hemorrhages into the airspace when platelet depletion was initiated 3 dpi compared to mice where platelets were depleted prior to infection. In addition, in dsRNA-induced ARDS model, platelet depletion resulted in increased signs of lung dysfunction, increased lung injury and local inflammation compared to mice with normal platelet levels. In conclusion, depletion of platelets after IAV infection resulted in increased alveolar hemorrhage and was associated with more pronounced lung inflammation, injury, and lung dysfunction. Our study suggests that interfering with platelet before viral infection can be beneficial as it limits the role of platelets as potential multiplicator of an initial pathologic immune reaction subsequently reducing collateral damage and organ dysfunction/failure. However, at later stages of viral infection, platelet activation is beneficial to facilitate tissue hemostasis as their absence later can result in increased hemorrhagic risk and more pronounced lung dysfunction. We aim to address the mechanism by which platelet contribute later to pathologic immune processes in dsRNA-induced or viral ARDS