Abstract
AbstractPlatelets have been identified with diverse functions in coagulation, host tissue repair, and immune activity. Lee and colleagues report another important finding related to platelet function in animal models of lung disease. They find platelets protect against lung injury from pathogen-secreted virulence factors.
Highlights
After IT inoculum of 106 colony-forming units (CFU) of Pseudomonas aeruginosa (PA), Mpl2/2 mice demonstrated rapid mortality; 8 of 8 Mpl2/2 mice died within 48 hours, whereas 7 of 8 littermate Mpl1/1 mice survived to 7 days (Figure 1A)
Mpl2/2 mice exposed to acute PA bacterial infection model demonstrate rapid mortality marked by lung injury and alveolar hemorrhage that is attenuated by partial platelet reconstitution
We found that PA SN caused lung epithelial cell death in a time-dependent manner in vitro (Figure 5C), and live-cell imaging of MLE cells exposed to PA SN revealed cellular blebbing and early annexin V staining, consistent with apoptosis, that later transitioned to propidium iodide staining (Figure 5D)
Summary
Acute respiratory distress syndrome (ARDS) is estimated to underlie 10% of intensive care unit admissions worldwide and cause 74 500 deaths annually in the United States.[1,2] The most common risk factor for ARDS is infection, primarily pneumonia and sepsis.[1,3] Platelet deficiency has consistently been associated with worse outcomes in ARDS, and a missense genetic variant in LRRC16A/CARMIL1 that limits reductions in platelet counts during ARDS is associated with improved patient survival.[4,5,6,7,8] it remains uncertain whether platelets can directly provide protection during lung injury.[9,10]. Submitted 21 September 2018; accepted 9 January 2019.
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