Intravascular hemolysis triggers ADP-mediated generation of platelet-rich thrombi in precapillary pulmonary arterioles

Brzóska, Tomasz; Vats, Ravi; Bennewitz, Margaret F.; Tutuncuoglu, Egemen; Watkins, Simon C.; Ragni, Margaret V.; Neal, Matthew D.; Gladwin, Mark T.; Sundd, Prithu

doi:10.1172/jci.insight.139437

Cited by 11 publications

(16 citation statements)

References 72 publications

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“…Data represent mean ± SE. *p < 0.05, **p < 0.01 for 0.5 mg/kg versus 2.5 mg/kg IV ADP (Brzoska et al, 2020).…”

Section: Image Analysismentioning

confidence: 96%

“…We recently reported that acute intravascular hemolysis in mice promotes adenosine diphosphate (ADP)−dependent platelet activation, leading to thrombosis in the precapillary pulmonary arterioles (Brzoska et al, 2020). Here, we describe how to acquire and analyze data to quantify platelet-dependent in situ pulmonary thrombosis.…”

Section: Quantification Of Platelet-dependent Pulmonary Thrombosismentioning

confidence: 99%

“…Quantification of platelet-dependent pulmonary thrombosis (Adapted from Brzoska et al, 2020). Platelets are shown in green and pulmonary microcirculation in purple.…”

Section: Figurementioning

confidence: 99%

“…The sizes of all the platelet-rich thrombi in a single image frame were added to generate total pulmonary thrombi area, which was plotted as a function of time. Changes in total pulmonary thrombi area over time served to calculate pulmonary thrombi maximum area and area under the curve (Brzoska et al, 2020).…”

Section: Figurementioning

confidence: 99%

“…We have also used qFILM to show that tissue factor inhibition also reduces pulmonary arteriole micro‐embolism by neutrophil‐platelet aggregates in SCD mice (Sparkenbaugh et al., 2020). Most recently, we utilized qFILM to demonstrate that acute intravascular hemolysis triggers ADP‐mediated platelet‐dependent in situ pulmonary thrombosis in mice (Brzoska et al., 2020) (see Fig. 7).…”

Section: Commentarymentioning

confidence: 99%

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Live Imaging of the Lung

et al. 2020

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Live imaging is critical to determining the dynamics and spatial interactions of cells within the tissue environment. In the lung, this has proven to be difficult due to the motion brought about by ventilation and cardiac contractions. A previous version of this Current Protocols in Cytometry article reported protocols for imaging ex vivo live lung slices and the intact mouse lung. Here, we update those protocols by adding new methodologies, new approaches for quantitative image analysis, and new areas of potential application.

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“…Data represent mean ± SE. *p < 0.05, **p < 0.01 for 0.5 mg/kg versus 2.5 mg/kg IV ADP (Brzoska et al, 2020).…”

Section: Image Analysismentioning

confidence: 96%

Section: Quantification Of Platelet-dependent Pulmonary Thrombosismentioning

confidence: 99%

“…Quantification of platelet-dependent pulmonary thrombosis (Adapted from Brzoska et al, 2020). Platelets are shown in green and pulmonary microcirculation in purple.…”

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Commentarymentioning

confidence: 99%

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Live Imaging of the Lung

et al. 2020

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Neutrophils and galectin-3 defend mice from lethal bacterial infection and humans from acute respiratory failure

Das,

Kaminski,

Schlegel

et al. 2024

Nat Commun

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Respiratory infection by Pseudomonas aeruginosa, common in hospitalized immunocompromised and immunocompetent ventilated patients, can be life-threatening because of antibiotic resistance. This raises the question of whether the host’s immune system can be educated to combat this bacterium. Here we show that prior exposure to a single low dose of lipopolysaccharide (LPS) protects mice from a lethal infection by P. aeruginosa. LPS exposure trained the innate immune system by promoting expansion of neutrophil and interstitial macrophage populations distinguishable from other immune cells with enrichment of gene sets for phagocytosis- and cell-killing-associated genes. The cell-killing gene set in the neutrophil population uniquely expressed Lgals3, which encodes the multifunctional antibacterial protein, galectin-3. Intravital imaging for bacterial phagocytosis, assessment of bacterial killing and neutrophil-associated galectin-3 protein levels together with use of galectin-3-deficient mice collectively highlight neutrophils and galectin-3 as central players in LPS-mediated protection. Patients with acute respiratory failure revealed significantly higher galectin-3 levels in endotracheal aspirates (ETAs) of survivors compared to non-survivors, galectin-3 levels strongly correlating with a neutrophil signature in the ETAs and a prognostically favorable hypoinflammatory plasma biomarker subphenotype. Taken together, our study provides impetus for harnessing the potential of galectin-3-expressing neutrophils to protect from lethal infections and respiratory failure.

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A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical vessels

Shaked

Foo

et al. 2022

Preprint

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How transient hyperglycemia contributes to cerebro-vascular disease has been a challenge to study under controlled conditions. We present an approach to model luminal vessel thrombo-inflammation using amplified, ultrashort laser-pulses to physically disrupt brain-venule endothelium. Vessel disruption in conjunction with transient hyperglycemia from a single injection of metabolically active D glucose results in real-time responses to venule damage that include rapid serum extravasation, platelet aggregation, and neutrophil recruitment, in normal mice. In contrast, vessel thrombo-inflammation following laser-induced vessel disruption is significantly reduced in mice injected with metabolically inert L-glucose. Thrombo-inflammation is pharmacologically ameliorated by a platelet inhibitor, by a scavenger of reactive oxygen species, or by a nitric oxide donor. For comparison, in diabetic mice injured vessel thrombo-inflammatory responses are also reduced by restoration of normo-glycemia. Our approach provides a controlled method to probe synergies of transient metabolic and physical vascular perturbations and reveals new aspects of brain pathophysiology.

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Intravascular hemolysis triggers ADP-mediated generation of platelet-rich thrombi in precapillary pulmonary arterioles

Cited by 11 publications

References 72 publications

Live Imaging of the Lung

Live Imaging of the Lung

Neutrophils and galectin-3 defend mice from lethal bacterial infection and humans from acute respiratory failure

A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical vessels

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