PB0798 - Role of platelets in maintain lung hemostasis during dsRNA-induced acute respiratory distress syndrome (ARDS) in mice.

Background: Platelets are sentinels for vascular injury and play an important role in hemostasis. Platelets maintain integrity of vasculature in case of inflammation-induced vascular injury by making platelet plugs at holes left by transmigrating neutrophils. Respiratory RNA viruses cause severe lung pathology and are associated with platelet activation and thrombosis. PolyIC can be used to create dsRNA-induced ARDS.

Aims: To study role of platelets in dsRNA-induced ARDS in mice.

Methods: Wild-type mice treated with polyIC (100µg, intranasally) for one day or daily for 3 days to induce acute and chronic ARDS. Mice were treated intravenously with R300 to deplete platelets or control IgG at day 0 and day 2 prior to polyIC administration. Lung function was recorded, plasma and bronchoalveolar lavage fluid (BALF) were collected before and after 3 days of treatment. BALF cellularity and blood cellular composition was analyzed. Markers of lung injury and cytokines/chemokines were measured in BALF and plasma

Results: PolyIC treatment leads to local lung inflammation, coagulation activation and ARDS-like lung dysfunction. Mice treated with R300 antibody showed severe thrombocytopenia (95-97% platelet depletion) and exhibited impaired alveolar hemostasis and increased hemorrhages into the airspace on both day 1 and day 3 of poly IC treatment compared to the IgG controls. In addition, platelet-depleted mice showed increased signs of dsRNA-induced ARDS measured by reduced lung function, increased lung injury markers and local inflammation compared to IgG control mice after polyIC treatment.

Conclusion(s): Platelets are important in maintaining lung function in dsRNA-induced ARDS. Lack of platelets resulted in increased alveolar hemorrhage associated with more pronounced lung inflammation, injury, and lung dysfunction. Interfering with platelet activation during viral infections might result in increased bleeding risk and more pronounced lung dysfunction. If platelet contribute later to pathologic immune processes in dsRNA-induced or viral ARDS are under investigation.