ArticleBritish journal of pharmacology2015
Platelet secretion of CXCL4 is Rac1-dependent and regulates neutrophil infiltration and tissue damage in septic lung damage.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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.
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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
31 citing papers in PubMed, 46 citations in OpenAlex.
- Tumor-derived RAC1Science advances · 2025Article
- SPI1 triggers the formation of neutrophil extracellular traps in multiple sclerosis through CXCL4.Journal of molecular histology · 2025Article
- Inhibiting Rac1 signaling alleviates DSS-induced colitis by improving inflammatory response and intestinal permeability.Gastroenterology report · 2025Article
- Platelet Factor 4: A Mysterious Chemokine in Inflammatory Regulation Diseases.Journal of inflammation research · 2025Review
- Liver ischaemia-reperfusion injury: a new understanding of the role of innate immunity.Nature reviews. Gastroenterology & hepatology · 2022Review
- Hepatic Ischemia-reperfusion Injury in Mice was Alleviated by Rac1 Inhibition - More Than Just ROS-inhibition.Journal of clinical and translational hepatology · 2022Article
- Platelets mediate trained immunity against bone and joint infections in a mouse model.Bone & joint research · 2022Article
- One Shoot, Two Birds: Alleviating Inflammation Caused by Ischemia/Reperfusion Injury to Reduce the Recurrence of Hepatocellular Carcinoma.Frontiers in immunology · 2022Review
- Bacterial polyphosphates induce CXCL4 and synergize with complement anaphylatoxin C5a in lung injury.Frontiers in immunology · 2022Article
- CCL25 Inhibition Alleviates Sepsis-Induced Acute Lung Injury and Inflammation.Infection and drug resistance · 2022Article
- Article
- Platelet biology of the rapidly failing lung.British journal of haematology · 2020Review
- CXCL4 Links Inflammation and Fibrosis by Reprogramming Monocyte-Derived Dendritic CellsFrontiers in immunology · 2020Article
- The road to lysosome-related organelles: Insights from Hermansky-Pudlak syndrome and other rare diseases.Traffic (Copenhagen, Denmark) · 2019Review
- Regulation of Innate Immune Responses by Platelets.Frontiers in immunology · 2019Review
- Human Platelet Protein Ubiquitylation and Changes following GPVI Activation.Thrombosis and haemostasis · 2019Article
- Platelet Factor 4 Attenuates Experimental Acute Liver Injury in Mice.Frontiers in physiology · 2019Article
- Nox2 Regulates Platelet Activation and NET Formation in the Lung.Frontiers in immunology · 2019Article
- Platelets in Sepsis: An Update on Experimental Models and Clinical Data.Frontiers in immunology · 2019Review
- Measuring and interpreting platelet-leukocyte aggregates.Platelets · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposePlatelets are potent regulators of neutrophil accumulation in septic lung damage. We hypothesized that platelet-derived CXCL4 might support pulmonary neutrophilia in a murine model of abdominal sepsis. EXPERIMENTAL APPROACH: Polymicrobial sepsis was triggered by coecal ligation and puncture (CLP) in C57BL/6 mice. Platelet secretion of CXCL4 was studied by using confocal microscopy. Plasma and lung levels of CXCL4, CXCL1 and CXCL2 were determined by elisa. Flow cytometry was used to examine surface expression of Mac-1 on neutrophils. KEY
resultsCLP increased CXCL4 levels in plasma, and platelet depletion reduced plasma levels of CXCL4 in septic animals. Rac1 inhibitor NSC23766 decreased the CLP-enhanced CXCL4 in plasma by 77%. NSC23766 also abolished PAR4 agonist-induced secretion of CXCL4 from isolated platelets. Inhibition of CXCL4 reduced CLP-evoked neutrophil recruitment, oedema formation and tissue damage in the lung. However, immunoneutralization of CXCL4 had no effect on CLP-induced expression of Mac-1 on neutrophils. Targeting CXCL4 attenuated plasma and lung levels of CXCL1 and CXCL2 in septic mice. CXCL4 had no effect on neutrophil chemotaxis in vitro, indicating it has an indirect effect on pulmonary neutrophilia. Intratracheal CXCL4 enhanced infiltration of neutrophils and formation of CXCL2 in the lung. CXCR2 antagonist SB225002 markedly reduced CXCL4-provoked neutrophil accumulation in the lung. CXCL4 caused secretion of CXCL2 from isolated alveolar macrophages. CONCLUSIONS AND IMPLICATIONS: Rac1 controls platelet secretion of CXCL4 and CXCL4 is a potent stimulator of neutrophil accumulation in septic lungs via generation of CXCL2 in alveolar macrophages. Platelet-derived CXCL4 plays an important role in lung inflammation and tissue damage in polymicrobial sepsis.
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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.