ArticleLeukemia2012
Conditioning for hematopoietic transplantation activates the complement cascade and induces a proteolytic environment in bone marrow: a novel role for bioactive lipids and soluble C5b-C9 as homing factors.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 131 citations in OpenAlex.
- UDP-Glucose-P2Y14 Receptor Signaling Enhances the Responsiveness of Hematopoietic Stem/Progenitor Cells to Chemoattractants by Facilitating Membrane Lipid Raft Formation and Nlrp3 Inflammasome Activation.Stem cell reviews and reports · 2026Article
- The NLRP3 Inflammasome Transmits Sterile Inflammation Signals to Sustain Proper Mitochondrial Electron Transport Chain Function and Influences Cellular Metabolism.Stem cell reviews and reports · 2025Article
- Role of Ceramide Kinase/C1P in the Regulation of Cell Growth and Survival.International journal of molecular sciences · 2025Review
- Complosome as a new intracellular regulatory network in both normal and malignant hematopoiesis.Leukemia · 2025Review
- Hematopoietic stem cells on the crossroad between purinergic signaling and innate immunity.Purinergic signalling · 2025Review
- Molecular Deconvolution of Bone Marrow Adipose Tissue Interactions with Malignant Hematopoiesis: Potential for New Therapy Development.Current osteoporosis reports · 2024Review
- Sphingolipid Signaling and Complement Activation in Glioblastoma: A Promising Avenue for Therapeutic Intervention.BioChem · 2024Article
- Hematopoiesis Revolves Around the Primordial Evolutional Rhythm of Purinergic Signaling and Innate Immunity - A Journey to the Developmental Roots.Stem cell reviews and reports · 2024Review
- Article
- The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype.Frontiers in immunology · 2023Article
- Crosstalk between pro-survival sphingolipid metabolism and complement signaling induces inflammasome-mediated tumor metastasis.Cell reports · 2022Article
- Myeloablative Conditioning for Transplantation Induces State of Sterile Inflammation in the Bone Marrow: Implications for Optimizing Homing and Engraftment of Hematopoietic Stem Cells.Antioxidants & redox signaling · 2022Review
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Novel Evidence That Alternative Pathway of Complement Cascade Activation is Required for Optimal Homing and Engraftment of Hematopoietic Stem/progenitor Cells.Stem cell reviews and reports · 2022Article
- Hematopoiesis and innate immunity: an inseparable couple for good and bad times, bound together by an hormetic relationship.Leukemia · 2022Review
- Article
- Role of Sphingolipids in Multiple Myeloma Progression, Drug Resistance, and Their Potential as Therapeutic Targets.Frontiers in oncology · 2022Review
- Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells - Clinical and Translational Implications.Stem cell reviews and reports · 2021Review
- New insights into renal lipid dysmetabolism in diabetic kidney disease.World journal of diabetes · 2021Review
- CD11c regulates hematopoietic stem and progenitor cells under stress.Blood advances · 2020Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
We have observed that conditioning for hematopoietic transplantation by lethal irradiation induces a proteolytic microenvironment in the bone marrow (BM) that activates the complement cascade (CC). As a result, BM is enriched for proteolytic enzymes and the soluble form of the terminal product of CC activation, the membrane attack complex C5b-C9 (MAC). At the same time, proteolytic enzymes induced in irradiated BM impair the chemotactic activity of α-chemokine stromal-derived factor-1 (SDF-1). As SDF-1 is considered a crucial BM chemoattractant for transplanted hematopoietic stem/progenitor cells (HSPCs), we sought to determine whether other factors that are resistant to proteolytic enzymes have a role in this process, focusing on proteolysis-resistant bioactive lipids. We found that the concentrations of sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) increase in the BM after conditioning for transplantation and that both S1P and, as we show here for the first time, C1P are potent chemoattractants for HSPCs. Next, we observed that C5-deficient mice that do not generate MAC show impaired engraftment of HSPCs. In support of a role for MAC in homing and engraftment, we found that soluble MAC enhances in a CR3 (CD11b/CD18)-dependent manner the adhesion of HSPCs to BM stromal cells and increases the secretion of SDF-1 by BM stroma. We conclude that an increase in BM levels of proteolytic enzyme-resistant S1P and C1P and activation of CC, which leads to the generation of MAC, has an important and previously underappreciated role in the homing of transplanted HSPCs.
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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.