von Willebrand factor (VWF) levels are elevated and a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 (ADAMTS13) activity is decreased in both acute and chronic inflammation. We hypothesized that by cleaving hyperactive ultralarge VWF (ULVWF) multimers, ADAMTS13 down-regulates both thrombosis and inflammation. Using intravital microscopy, we show that ADAMTS13 deficiency results in increased leukocyte rolling on unstimulated veins and increased leukocyte adhesion in inflamed veins. Both processes were dependent on the presence of VWF. Depletion of platelets in Adamts13(-/-) mice reduced leukocyte rolling, suggesting that platelet interaction with ULVWF contributes to this process. Increased levels of endothelial P-selectin and plasma VWF in Adamts13(-/-) compared with wild-type (WT) mice indicated an elevated release of Weibel-Palade bodies. ULVWF multimers released upon stimulation with histamine, a secretagogue of Weibel-Palade bodies, slowed down leukocyte rolling in Adamts13(-/-) but not in WT mice. Furthermore, in inflammatory models, ADAMTS13 deficiency resulted in enhanced extravasation of neutrophils, and this process was also dependent on VWF. Our findings reveal an important role for ADAMTS13 in preventing excessive spontaneous Weibel-Palade body secretion, and in the regulation of leukocyte adhesion and extravasation during inflammation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526201 | PMC |
| http://dx.doi.org/10.1084/jem.20080130 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CRP deposition in human abdominal aortic aneurysm is associated with transcriptome alterations toward aneurysmal pathogenesis: insights from spatial whole transcriptomic analysis.
Front Immunol
December 2024
Department of Thoracic and Cardiovascular Surgery, Seoul Metropolitan Government-Seoul National University (SMG-SNU) Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
Background: We investigated the effects of C-reactive protein (CRP) deposition on the vessel walls in abdominal aortic aneurysm (AAA) by analyzing spatially resolved changes in gene expression. Our aim was to elucidate the pathways that contribute to disease progression.
Methods: AAA specimens from surgically resected formalin-fixed paraffin-embedded tissues were categorized into the AAA-high CRP [serum CRP ≥ 0.
Targeting P-selectin and interleukin-1β in mice with sickle cell disease: effects on vaso-occlusion, liver injury and organ iron deposition.
Haematologica
November 2024
Hematology Center, University of Campinas - UNICAMP, Campinas - São Paulo.
Continuous vaso-occlusive and inflammatory processes cause extensive end-organ damage in adults with sickle cell disease (SCD), and there is little evidence that longterm hydroxyurea therapy prevents this. In initial trials, P-selectin blockade with crizanlizumab reduced SCD vaso-occlusive crisis frequency, and interleukin (IL)-1β inhibition in SCD patients, using canakinumab, lowered inflammatory markers. We used murine SCD models to examine the effects of acute and chronic blockade of Pselectin and of IL-1β on vaso-occlusive events, their inflammatory profile and organ health.
View Article and Find Full Text PDFType 2 diabetes remodels collateral circulation and promotes leukocyte adhesion following ischemic stroke.
bioRxiv
October 2024
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Article Synopsis
- Type 2 diabetes mellitus (T2DM) leads to smaller pial vessels and lower blood flow velocity before and after a stroke, contributing to poor recovery outcomes.
- After a stroke, T2DM mice showed persistent deficits in blood flow and increased leukocyte adhesion to blood vessel walls, highlighting chronic inflammation's role in complicating recovery.
- The study used two-photon microscopy to analyze blood flow dynamics, vessel remodeling, and inflammation in the brain, suggesting that T2DM-induced changes worsen stroke effects.
Gingival inflammation and leukocyte-endothelium cell interactions in women with polycystic ovary syndrome.
J Periodontol
October 2024
Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research, Valencia, Spain.
Article Synopsis
- This study explores the impact of gingivitis on inflammation and cardiovascular risks in women with polycystic ovary syndrome (PCOS).
- The research involved three groups of participants: two with PCOS (one with gingivitis and one without) and a control group, all assessed for various health indicators and inflammatory markers.
- Results indicated that PCOS patients, especially those with gingivitis, had higher levels of systemic inflammation and more aggressive neutrophil behavior, which may increase the risk of atherosclerosis.
Visualization of Neutrophil Extracellular Traps in Mesenteric Venules After Mesenteric Ischemia-Reperfusion Injury via Intravital Microscopy.
J Vis Exp
September 2024
Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main;
Article Synopsis
- Intestinal ischemia-reperfusion (I/R) injury is a severe condition caused by reduced blood flow to the intestines, leading to significant tissue damage and poor health outcomes.
- The study uses a microsurgical model combined with intravital microscopy to observe the behaviors of immune cells (like leukocytes) during I/R injury, particularly focusing on the role of the endothelial PAR1 receptor.
- Results show that mice lacking the PAR1 receptor had less leukocyte adhesion and reduced formation of neutrophil extracellular traps (NETs), suggesting that PAR1 is a critical factor in the inflammatory response during I/R injury.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!