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Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli. | LitMetric

AI Article Synopsis

  • This study investigates how sickle cell disease (SCD) causes blockages in lung blood vessels, leading to lung injuries during crises.
  • Researchers used advanced imaging in mice with SCD and found that neutrophils and platelets form clumps that block tiny lung arteries and worsen the condition.
  • Targeting specific molecules on platelets may offer a new treatment approach to prevent lung complications in SCD patients by reducing these harmful aggregates.

Article Abstract

In patients with sickle cell disease (SCD), the polymerization of intraerythrocytic hemoglobin S promotes downstream vaso-occlusive events in the microvasculature. While vaso-occlusion is known to occur in the lung, often in the context of systemic vaso-occlusive crisis and the acute chest syndrome, the pathophysiological mechanisms that incite lung injury are unknown. We used intravital microscopy of the lung in transgenic humanized SCD mice to monitor acute vaso-occlusive events following an acute dose of systemic lipopolysaccharide sufficient to trigger events in SCD but not control mice. We observed cellular microembolism of precapillary pulmonary arteriolar bottlenecks by neutrophil-platelet aggregates. Blood from SCD patients was next studied under flow in an in vitro microfluidic system. Similar to the pulmonary circulation, circulating platelets nucleated around arrested neutrophils, translating to a greater number and duration of neutrophil-platelet interactions compared with normal human blood. Inhibition of platelet P-selectin with function-blocking antibody attenuated the neutrophil-platelet interactions in SCD patient blood in vitro and resolved pulmonary arteriole microembolism in SCD mice in vivo. These results establish the relevance of neutrophil-platelet aggregate formation in lung arterioles in promoting lung vaso-occlusion in SCD and highlight the therapeutic potential of targeting platelet adhesion molecules to prevent acute chest syndrome.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214368PMC
http://dx.doi.org/10.1172/jci.insight.89761DOI Listing

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