ArticleAmerican journal of hematology2019
Critical role of C5a in sickle cell disease.
Article in American journal of hematology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 63 citations in OpenAlex.
- Proteomic Analysis of Golden Sputum Reveals Pulmonary Complement Activation During Acute Chest Syndrome in Children With Sickle Cell Disease.American journal of hematology · 2026Article
- Comprehensive analysis of complement activation in a hydroxyurea-treated patient cohort with sickle cell disease.Blood advances · 2026Article
- Review
- Emerging pathways in thromboinflammation of sickle cell disease: novel findings in disease pathogenesis.Research and practice in thrombosis and haemostasis · 2025Review
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- Complement is activated in patients with acute chest syndrome caused by sickle cell disease and represents a therapeutic target.Science translational medicine · 2025Article
- Transcriptomic atlas reveals organ-specific disease tolerance in sickle cell mice.Blood advances · 2025Article
- Behavioral and transcriptional effects of age in HbSS-BERK humanized SCD mice.Journal of sickle cell disease · 2025Article
- Thromboembolic Events in the Era of COVID-19: A Detailed Narrative Review.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2025Review
- Review
- Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms.International journal of molecular sciences · 2024Review
- Can we use biomarkers to identify those at risk of acute pain from sickle cell disease?Expert review of hematology · 2024Review
- Subcutaneous injection of IHP-102 prevents lung vaso-occlusion in sickle cell disease mice.Haematologica · 2024Article
- Coagulation and platelet biology at the intersection of health and disease: illustrated capsules of the 11th Symposium on Hemostasis at the University of North Carolina.Research and practice in thrombosis and haemostasis · 2024Article
- Mouse models of sickle cell disease: Imperfect and yet very informative.Blood cells, molecules & diseases · 2024Review
- Cold exposure induces vaso-occlusion and pain in sickle mice that depend on complement activation.Blood · 2023Article
- A Review of the Relationship between the Immune Response, Inflammation, Oxidative Stress, and the Pathogenesis of Sickle Cell Anaemia.Biomedicines · 2023Review
- Management of Older Adults with Sickle Cell Disease: Considerations for Current and Emerging Therapies.Drugs & aging · 2023Review
- Increased Susceptibility for Adverse Reactions to Ultrasound Enhancing Agents in Sickle Cell Disease.Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography · 2023Article
- The BACH1 inhibitor ASP8731 inhibits inflammation and vaso-occlusion and induces fetal hemoglobin in sickle cell disease.Frontiers in medicine · 2023Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Innate immune complement activation may contribute to sickle cell disease (SCD) pathogenesis. Ischemia-reperfusion physiology is a key component of the inflammatory and vaso-occlusive milieu in SCD and is associated with complement activation. C5a is an anaphylatoxin, a potent pro-inflammatory mediator that can activate leukocytes, platelets, and endothelial cells, all of which play a role in vaso-occlusion. We hypothesize that hypoxia-reoxygenation (H/R) in SCD mice activates complement, promoting inflammation and vaso-occlusion. At baseline and after H/R, sickle Townes-SS mice had increased C3 activation fragments and C5b-9 deposition in kidneys, livers and lungs and alternative pathway Bb fragments in plasma compared to control AA-mice. Activated complement promoted vaso-occlusion (microvascular stasis) in SS-mice; infusion of zymosan-activated, but not heat-inactivated serum, induced substantial vaso-occlusion in the skin venules of SS-mice. Infusion of recombinant C5a induced stasis in SS, but not AA-mice that was blocked by anti-C5a receptor (C5aR) IgG. C5a-mediated stasis was accompanied by inflammatory responses in SS-mice including NF-κB activation and increased expression of TLR4 and adhesion molecules VCAM-1, ICAM-1, and E-selectin in the liver. Anti-C5aR IgG blocked these inflammatory responses. Also, C5a rapidly up-regulated Weibel-Palade body P-selectin and von Willebrand factor on the surface of human umbilical vein endothelial cells in vitro and on vascular endothelium in vivo. In SS-mice, a blocking antibody to P-selectin inhibited C5a-induced stasis. Similarly, an antibody to C5 that blocks murine C5 cleavage or an antibody that blocks C5aR inhibited H/R-induced stasis in SS-mice. These results suggest that inhibition of C5a may be beneficial in SCD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.