Role of neutrophils in pulmonary vaso‐occlusion during sickle cell disease acute chest syndrome (669.6)

Abstract

Sickle cell disease (SCD) is a hematological disorder that leads to sickling of red blood cells within the microcirculation. The sickle red blood cells (sRBCs) are not only less deformable, but also express α4β1, ICAM‐4, Sialyl Lewis X and glycolipids not expressed on non SCD‐RBCs. These rigid sRBCs can get sequestered in the microcirculation to cause painful vaso‐occlusive crisis (VOC) in SCD patients. In the lung, VOC can contribute to acute chest syndrome, which is a form of acute lung injury. Several factors including the pro‐adhesive sRBCs, the large marginated pool of neutrophils, and the hyper‐inflammatory state present in SCD can contribute to pulmonary VOC. Although neutrophil‐RBC‐endothelium interactions are known to play a role in systemic VOC, the cellular mechanism that drives pulmonary VOC remains unknown. Intravital study of the lung microcirculation of live BERK or Townes SCD mice is conducted using two‐photon microscopy. Prior to observation, mice are challenged with lipopolysaccharide or PBS to cause lung inflammation and administered (iv) with fluorescent anti‐mouse Gr‐1 and Ter‐119 antibodies to label circulating neutrophils and RBCs, respectively. Vaso‐occlusion is defined as cellular aggregation and stasis of blood flow within the lumen of pulmonary capillaries. Preliminary results reveal that circulating macro‐aggregates of neutrophils and RBCs may play a role in pulmonary VOC.Grant Funding Source: Supported by AHA, VMI startup account, and NIH Pulmonary T32 training grant