ArticleBlood2009
Recombinant human activated protein C inhibits integrin-mediated neutrophil migration.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
43 citing papers in PubMed, 91 citations in OpenAlex.
- Targeting the interactions between neutrophils and microglia: a novel strategy for anti-inflammatory treatment of stroke.Acta pharmacologica Sinica · 2026Review
- Protein C in adult patients with sepsis: from pathophysiology to monitoring and supplementation.Journal of anesthesia, analgesia and critical care · 2025Review
- Integrins in the kidney - beyond the matrix.Nature reviews. Nephrology · 2025Review
- Loss of protein C vs protein S results in discrepant thrombotic phenotypes.Blood advances · 2025Article
- Thrombomodulin: A key regulator of intravascular blood coagulation, fibrinolysis, and inflammation, and a treatment for disseminated intravascular coagulation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- A synthetic bioactive peptide of the C-terminal fragment of adhesion protein Fibulin7 attenuates the inflammatory functions of innate immune cells in LPS-induced systemic inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Podocyte Integrin-Journal of the American Society of Nephrology : JASN · 2020Article
- Therapeutic Role of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis.Medicina (Kaunas, Lithuania) · 2019Review
- Extended live-tracking and quantitative characterization of wound healing and cell migration with SiR-Hoechst.Experimental cell research · 2018Article
- Review
- Regulation of immune cell signaling by activated protein C.Journal of leukocyte biology · 2018Review
- Sensing of Vascular Permeability in Inflamed Vessel of Live Animal.Journal of analytical methods in chemistry · 2018Article
- The Role of Gap Junction-Mediated Endothelial Cell-Cell Interaction in the Crosstalk between Inflammation and Blood Coagulation.International journal of molecular sciences · 2017Review
- Activated Protein C Attenuates Severe Inflammation by Targeting VLA-3Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Activated protein C inhibits neutrophil extracellular trap formationThe Journal of biological chemistry · 2017Article
- Activated protein C binds directly to Tie2: possible beneficial effects on endothelial barrier function.Cellular and molecular life sciences : CMLS · 2017Article
- The Vitamin E Analog Gamma-Tocotrienol (GT3) and Statins Synergistically Up-Regulate Endothelial Thrombomodulin (TM).International journal of molecular sciences · 2016Article
- Role of cellular events in the pathophysiology of sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2016Review
- Physiological cerebrovascular remodeling in response to chronic mild hypoxia: A role for activated protein C.Experimental neurology · 2016Article
- Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice.Blood · 2015Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Integrin-mediated cell migration is central to many biologic and pathologic processes. During inflammation, tissue injury results from excessive infiltration and sequestration of activated leukocytes. Recombinant human activated protein C (rhAPC) has been shown to protect patients with severe sepsis, although the mechanism underlying this protective effect remains unclear. Here, we show that rhAPC directly binds to beta(1) and beta(3) integrins and inhibits neutrophil migration, both in vitro and in vivo. We found that human APC possesses an Arg-Gly-Asp (RGD) sequence, which is critical for the inhibition. Mutation of this sequence abolished both integrin binding and inhibition of neutrophil migration. In addition, treatment of septic mice with a RGD peptide recapitulated the beneficial effects of rhAPC on survival. Thus, we conclude that leukocyte integrins are novel cellular receptors for rhAPC and the interaction decreases neutrophil recruitment into tissues, providing a potential mechanism by which rhAPC may protect against sepsis.
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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.