ArticleLeukemia2009
Impaired mobilization of hematopoietic stem/progenitor cells in C5-deficient mice supports the pivotal involvement of innate immunity in this process and reveals novel promobilization effects of granulocytes.
Article in Leukemia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 138 citations in OpenAlex.
- The CXCR4 and adhesion molecule expression of CD34+ hematopoietic cells mobilized by "on-demand" addition of plerixafor to granulocyte-colony-stimulating factor.Transfusion · 2014Trial
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- Complosome as a new intracellular regulatory network in both normal and malignant hematopoiesis.Leukemia · 2025Review
- Complosome Regulates Hematopoiesis at the Mitochondria Level.Stem cell reviews and reports · 2025Article
- Hematopoietic stem cells on the crossroad between purinergic signaling and innate immunity.Purinergic signalling · 2025Review
- Neutrophils in Rheumatoid Arthritis Synovium: Implications on Disease Activity and Inflammation State.Journal of inflammation research · 2025Article
- The Different Responsiveness of C3- and C5-deficient Murine BM Cells to Oxidative Stress Explains Why C3 Deficiency, in Contrast to C5 Deficiency, Correlates with Better Pharmacological Mobilization and Engraftment of Hematopoietic Cells.Stem cell reviews and reports · 2025Article
- Inflammasomes: potential therapeutic targets in hematopoietic stem cell transplantation.Cell communication and signaling : CCS · 2024Review
- Complement or insult: the emerging link between complement cascade deficiencies and pathology of myeloid malignancies.Journal of leukocyte biology · 2024Review
- 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
- The Relationship between Complement ComponentsGenes · 2023Article
- Zymosan A Improved Doxorubicin-Induced Ventricular Remodeling by Evoking Heightened Cardiac Inflammatory Responses and Healing in Mice.Journal of the American Heart Association · 2023Article
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- Hematopoiesis and innate immunity: an inseparable couple for good and bad times, bound together by an hormetic relationship.Leukemia · 2022Review
- R4 RGS proteins suppress engraftment of human hematopoietic stem/progenitor cells by modulating SDF-1/CXCR4 signaling.Blood advances · 2021Article
- Article
- 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
- Nlrp3 Inflammasome Signaling Regulates the Homing and Engraftment of Hematopoietic Stem Cells (HSPCs) by Enhancing Incorporation of CXCR4 Receptor into Membrane Lipid Rafts.Stem cell reviews and reports · 2020Article
- Pannexin-1 channel "fuels" by releasing ATP from bone marrow cells a state of sterile inflammation required for optimal mobilization and homing of hematopoietic stem cells.Purinergic signalling · 2020Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
We reported that complement cascade (CC) becomes activated in bone marrow (BM) during granulocyte colony-stimulating factor (G-CSF) mobilization of hematopoietic stem/progenitor cells (HSPCs) and showed that, although third CC component (C3)-deficient mice are easy mobilizers, fifth CC component (C5)-deficient mice mobilize very poorly. To explain this, we postulated that activation/cleavage of CC releases C3a and C5a anaphylatoxins that differently regulate mobilization. Accordingly, C3a, by enhancing responsiveness of HSPCs to decreasing concentrations of stromal-derived growth factor-1 (SDF-1) in BM, prevents mobilization and promotes their BM retention. Therefore, in this study, we focused on the mobilization-enhancing role of C5a. We found that C5a receptor (C5aR) is not expressed on the surface of HSPCs, and that C5a-mediated promobilization effects are mediated by stimulation of granulocytes. Overall, our data support the following model. First C5aR(+) granulocytes are chemoattracted by plasma C5 cleavage fragments, being the first wave of cells leaving BM. This facilitates a subsequent egress of HSPCs. In the next step, after leaving BM, granulocytes undergo degranulation in response to plasma C5a and secrete some cationic peptides (cathelicidin, beta-defensin) that, as shown here for the first time, highly enhance the responsiveness of HSPCs to plasma SDF-1 gradient. In conclusion, our data reveal the underappreciated central role of innate immunity in mobilization, in which C5 cleavage fragments through granulocytes orchestrate this process.
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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.