ArticlePNAS nexus2024
Signaling-biophysical modeling unravels mechanistic control of red blood cell phagocytosis by macrophages in sickle cell disease.
Article in PNAS nexus, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- A Multiscale Signaling-Biophysical Framework Reveals Mechanisms of Macrophage-Mediated RBC Clearance in Sickle Cell and Gaucher Disease.bioRxiv : the preprint server for biology · 2026Article
- Advances in engineering immune-tumor microenvironments on-a-chip: integrative microfluidic platforms for immunotherapy and drug discovery.Molecular cancer · 2025Review
- Organ-on-chip platforms for nanoparticle toxicity and efficacy assessment: Advancing beyond traditional in vitro and in vivo models.Materials today. Bio · 2025Review
- Hypoxia, Inflammation, and Cytokine Crosstalk in Sickle Cell Disease: From Mechanisms to Modulation- A Narrative Review.Pediatric health, medicine and therapeutics · 2025Review
- Biomechanics of phagocytosis of red blood cells by macrophages in the human spleen.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Red blood cell (RBC) aging manifests through progressive changes in cell morphology, rigidity, and expression of membrane proteins. To maintain the quality of circulating blood, splenic macrophages detect the biochemical signals and biophysical changes of RBCs and selectively clear them through erythrophagocytosis. In sickle cell disease (SCD), RBCs display alterations affecting their interaction with macrophages, leading to aberrant phagocytosis that may cause life-threatening spleen sequestration crises. To illuminate the mechanistic control of RBC engulfment by macrophages in SCD, we integrate a system biology model of RBC-macrophage signaling interactions with a biophysical model of macrophage engulfment, as well as in vitro phagocytosis experiments using the spleen-on-a-chip technology. Our modeling framework accurately predicts the phagocytosis dynamics of RBCs under different disease conditions, reveals patterns distinguishing normal and sickle RBCs, and identifies molecular targets including Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP1) and cluster of differentiation 47 (CD47)/signal regulatory protein α (SIRPα) as therapeutic targets to facilitate the controlled clearance of sickle RBCs in the spleen.
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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.