46 research outputs found
Replication Data for: Mechanism of platelet extracellular vesicle-mediated vaso-occlusion in Sickle Cell Disease
Experimental raw data file
sj-pdf-1-jcb-10.1177_0271678X231203023 - Supplemental material for A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules
Supplemental material, sj-pdf-1-jcb-10.1177_0271678X231203023 for A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules by Iftach Shaked, Conrad Foo, Philipp Mächler, Rui Liu, Yingying Cui, Xiang Ji, Thomas Broggini, Tomasz Kaminski, Suchita Suryakant Jadhav, Prithu Sundd, Michael Firer, Anna Devor, Beth Friedman and David Kleinfeld in Journal of Cerebral Blood Flow & Metabolism</p
A FLOW CHAMBER FOR CAPILLARY NETWORKS: LEUKOCYTE ADHESION IN CAPILLARY-SIZED, LIGAND-COATED MICROPIPETTES
Thrombo-Inflammation in COVID-19 and Sickle Cell Disease: Two Faces of the Same Coin
People with sickle cell disease (SCD) are at greater risk of severe illness and death from respiratory infections, including COVID-19, than people without SCD (Centers for Disease Control and Prevention, USA). Vaso-occlusive crises (VOC) in SCD and severe SARS-CoV-2 infection are both characterized by thrombo-inflammation mediated by endothelial injury, complement activation, inflammatory lipid storm, platelet activation, platelet-leukocyte adhesion, and activation of the coagulation cascade. Notably, lipid mediators, including thromboxane A2, significantly increase in severe COVID-19 and SCD. In addition, the release of thromboxane A2 from endothelial cells and macrophages stimulates platelets to release microvesicles, which are harbingers of multicellular adhesion and thrombo-inflammation. Currently, there are limited therapeutic strategies targeting platelet-neutrophil activation and thrombo-inflammation in either SCD or COVID-19 during acute crisis. However, due to many similarities between the pathobiology of thrombo-inflammation in SCD and COVID-19, therapies targeting one disease may likely be effective in the other. Therefore, the preclinical and clinical research spurred by the COVID-19 pandemic, including clinical trials of anti-thrombotic agents, are potentially applicable to VOC. Here, we first outline the parallels between SCD and COVID-19; second, review the role of lipid mediators in the pathogenesis of these diseases; and lastly, examine the therapeutic targets and potential treatments for the two diseases
In situ Microrheological Determination of Neutrophil Stiffening Following Adhesion in a Model Capillary
Abstract—There has been considerable debate on the relative importance of biochemical stimuli and mechanical deforma-tion in neutrophil adhesion in lung capillaries, a process observed following bacterial infection in the body. In contrast to venules, where the vessel diameter is larger than the leukocyte diameter (6–9 lm) and the adhesion process is better understood, in lung capillaries the vessel diameter (2–8 lm) is smaller than the leukocyte diameter. In this study, a micropipette was used as a model for the alveolar capillary microcirculation, allowing the effects of adhesion molecules (ICAM-1) on cell mechanical properties to be observed while applying a mechanical deformation. The microrheology technique that tracks the thermal motion of granules within neutrophils was used to extract the local intracellular viscoelastic moduli. Small regional differences in rheology were found, with the central body region being significantly stiffer than the leading end cap region. When cells were exposed to ICAM-1, the regional differences were preserved, but the viscoelastic moduli were moderately increased in all regions. These results are consistent with the literature on leukocyte sequestration and provide insight into the regional rheological effects of deformation and adhesion molecules on neutrophils
