Genna Ali Abdullah, Asangaedem Akpan, Marie M Phelan, Helen L Wright
{"title":"The complex role of neutrophils in healthy aging, inflammaging, and frailty.","authors":"Genna Ali Abdullah, Asangaedem Akpan, Marie M Phelan, Helen L Wright","doi":"10.1093/jleuko/qiaf117","DOIUrl":"10.1093/jleuko/qiaf117","url":null,"abstract":"<p><p>Immune function alters as we age, and is often accompanied by chronic, low-grade inflammation termed \"inflammaging.\" This leads cells to develop a senescence-associated secretory phenotype and release a range of proinflammatory cytokines and proteolytic enzymes. In individuals with frailty, inflammaging and senescence-associated secretory phenotype are increased, further reducing immune function and making individuals more susceptible to serious outcomes from infection. In this review, we focus on the role of neutrophils in healthy aging, inflammaging, and frailty. We summarize the key functions of neutrophils in an effective immune response to pathogens as well as discuss the important role of neutrophils in tissue repair and wound healing. We also discuss the decline in neutrophil immune responses associated with biological aging, in healthy older age and in individuals with frailty. We summarize the key role of metabolism and the antioxidant response in inflammatory neutrophil activation and identify the potential of therapeutics directed at longevity, metabolism, and cytokine signaling for the treatment of inflammaging.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dechang Liu, Jia Wang, Yuancheng Wei, Hai Wu, Shengtao Yuan, Mei Yang, Li Sun
{"title":"Senescent cancer cells in immune surveillance and evasion: mechanisms and therapeutic implications.","authors":"Dechang Liu, Jia Wang, Yuancheng Wei, Hai Wu, Shengtao Yuan, Mei Yang, Li Sun","doi":"10.1093/jleuko/qiaf125","DOIUrl":"10.1093/jleuko/qiaf125","url":null,"abstract":"<p><p>Cellular senescence is a stress-induced program characterized by long-lasting cell cycle arrest and the secretion of bioactive and inflammatory molecules, which are collectively referred to as the senescence-associated secretory phenotype (SASP). Diverse stressors, including oncogene activation, chemotherapy, radiotherapy, and cytokine exposure, can induce cellular senescence in cancer cells. Senescent cancer cells (SnCs) can enhance immune responses and promote tumor immune surveillance. However, in the tumor microenvironment (TME), SnCs can also induce immune suppression, facilitating tumor growth and metastasis. Understanding the biological changes in SnCs and their impact on the immune system is essential. In this review, we discuss 3 mechanisms by which the immune system recognizes and eliminates SnCs, as well as 3 mechanisms that allow SnCs to evade immune surveillance. Finally, we explore cancer treatment strategies related to SnCs, including SnC-based vaccines and the \"one-two punch\" therapy.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie-France N Soucy, Mathieu P A Hébert, Jérémie A Doiron, David A Barnett, Simon G Lamarre, Etienne Hebert-Chatelain, Luc H Boudreau
{"title":"Platelet-derived microvesicles modulate the bioenergetic and inflammatory phenotype of human polymorphonuclear leukocytes.","authors":"Marie-France N Soucy, Mathieu P A Hébert, Jérémie A Doiron, David A Barnett, Simon G Lamarre, Etienne Hebert-Chatelain, Luc H Boudreau","doi":"10.1093/jleuko/qiaf119","DOIUrl":"10.1093/jleuko/qiaf119","url":null,"abstract":"<p><p>Platelets release microvesicles (PMVs) into the extracellular milieu upon activation. PMVs retain various platelet components, including functional mitochondria, and actively participate in intercellular communication with immune cells such as polymorphonuclear leukocytes (PMNs). PMVs have been known to modulate the inflammatory response of PMNs under normal physiological condition. Despite growing interest in the transfer of biological material between immune cells, the mitochondrial content shuttling from PMVs to PMNs and the resulting effects have remained unclear. Using freshly isolated PMVs from healthy and consenting donors, we demonstrate that PMVs modulate both the bioenergetic and inflammatory phenotypes of the recipient immune cell. We first confirmed the mitochondrial content transfer and then measured cell viability, mitochondrial respiration, and ATP production. Platelet-derived mitochondria were found associated with PMNs, consequently decreasing caspase-3 activity. PMVs increased mitochondrial activity and ATP levels in the recipient cell. Incubation of PMNs with PMVs containing nonfunctional mitochondria did not affect respiration and caspase-3 activity. This demonstrates that functional and active mitochondria are required for the PMVs to modulate the bioenergenetic phenotype of human PMNs. Finally, we detected the transfer of active 12-lipoxygenase and of cyclooxygenase-1 in the recipient cells, enzymes found specifically in PMVs, and an increase in the production of their respective inflammatory products. These findings suggest that platelet-derived mitochondria play a key role in enhancing the survival and inflammatory function of PMNs in inflammatory conditions.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexis Brantly, Kyle Yeakle, Michael J Bouchard, Peter J Gaskill, Michael R Nonnemacher
{"title":"The role of liver macrophages in viral liver pathogenesis.","authors":"Alexis Brantly, Kyle Yeakle, Michael J Bouchard, Peter J Gaskill, Michael R Nonnemacher","doi":"10.1093/jleuko/qiaf088","DOIUrl":"10.1093/jleuko/qiaf088","url":null,"abstract":"<p><p>Liver macrophages play important roles in the pathophysiology of liver fibrosis and hepatocellular carcinoma. However, liver macrophages are a heterogenous population and have differing roles in maintenance of liver function and response in disease. In a healthy liver, macrophages play a critical role in antigen processing, maintaining tolerance to the high levels of gut-derived bacterial products, and regulating inflammation through cytokine response. However, macrophages also play a critical role in liver pathology, specifically in the context of viral infection. The liver is targeted by multiple viruses, including human immunodeficiency virus, hepatitis B virus, and hepatitis C virus, which dysregulate macrophage functions to affect liver disease. Infection with any of these viruses is associated with increased risk of developing hepatocellular carcinoma, and coinfection further accelerates the progression to liver disease and cancer. However, the exact mechanisms by which liver macrophages contribute to disease in the context of viral infections are not well defined. This is a particularly acute issue in human immunodeficiency virus-infected populations, which have high incidence of hepatitis B virus and hepatitis C virus coinfection. To address this knowledge gap, this review describes the populations of macrophages in the liver, outlines the current models and limitations associated with the study of liver macrophages, discusses the function and role of liver macrophages in the context of viral infection, and describes the mechanisms by which these cells contribute to hepatocellular carcinoma and fibrosis. We then use this information to propose focus areas for the liver macrophage field to better address and resolve viral liver disease.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insulin-like growth factor-neutralizing antibodies for cancer therapy.","authors":"Qi Zhao, Jia Shen","doi":"10.1093/jleuko/qiaf122","DOIUrl":"10.1093/jleuko/qiaf122","url":null,"abstract":"<p><p>The insulin-like growth factor (IGF) axis is crucial for regulating cell growth, survival, and differentiation. While therapies targeting the IGF-1R have shown limited clinical success as single agents, the abnormal expression of its ligands, IGF-I and IGF-II, has been shown to contribute significantly to resistance against IGF-1R-targeted treatments. This review explores recent advancements in neutralizing antibodies against IGF-I and/or IGF-II, including monoclonal antibody, bispecific antibodies, and engineered antibody domains. These approaches have demonstrated promising therapeutic potential in preclinical cancer models and are currently being evaluated in early clinical trials. Furthermore, we address the rationale for future combination strategies to overcome treatment resistance.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pierre Godfrin, Pierrick Le Borgne, Jonathan Sabah, François Lefebvre, Gilles Kauffenstein, Cyrielle Brossard, Amandine Schnee, Pauline Trognon, Charles-Eric Lavoignet, Laure Abensur Vuillaume
{"title":"Eonisophil-to-lymphocyte ratio and early variation as predictors of severity and in-hospital mortality in patients admitted to the emergency department for SARS-CoV-2 infection.","authors":"Pierre Godfrin, Pierrick Le Borgne, Jonathan Sabah, François Lefebvre, Gilles Kauffenstein, Cyrielle Brossard, Amandine Schnee, Pauline Trognon, Charles-Eric Lavoignet, Laure Abensur Vuillaume","doi":"10.1093/jleuko/qiaf105","DOIUrl":"10.1093/jleuko/qiaf105","url":null,"abstract":"<p><p>Since its emergence in 2019, the study of biomarkers in COVID-19 has focused on predicting the course of this potentially fatal disease. The eosinophil-to-lymphocyte ratio (ELR) appears to be a new indicator of systemic inflammation, morbidity, and mortality in inflammatory, allergic, and cancer. The aim of our study was to determine the prognostic value of ELR and its early variation in predicting in-hospital mortality and severity in emergency department (ED) patients with SARS-CoV-2 infection. Between March 1 and April 30, 2020, we conducted a multicenter, retrospective study in 6 major hospitals in northeastern France. The cohort included patients with a confirmed diagnosis of SARS-CoV-2 infection (moderate-to-severe disease) hospitalized after admission to the ED. A total of 1,035 patients were included in this study. The ELR at 24 h (odds ratio: 0.0054; 95% confidence interval: 0.0001 to 0.2523; P = 0.008) was associated with severity of infection. The only biochemical factor significantly associated with mortality was ΔELR at 24 h (i.e. the difference between ELR values at 24 h and at admission) (odds ratio: 0.0305; 95% confidence interval: 0.0026 to 0.3626; P = 0.006) in univariate analysis. The best ELR threshold for predicting severity of infection was found with the ELR at 24 h with a result of 0.0007 (sensitivity 63.8%, specificity 61%), and for predicting mortality, ΔELR at 24 h found significant values with a threshold of -0.013 (sensitivity 77.4%, specificity 8.48%). In conclusion, ELR at 24 h after ED admission may be a potentially useful biomarker for early prediction of severity of SARS-CoV-2 infection, but its isolated use remains limited for mortality prediction.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leonie S Helder, Laszlo A Groh, Vasiliki Matzaraki, Rob Ter Horst, Gert Jan Scheffer, Leo A B Joosten, Mihai G Netea, Anaisa V Ferreira
{"title":"Bacillus Calmette-Guérin-induced trained immunity potentiates TH17 responses in vitro.","authors":"Leonie S Helder, Laszlo A Groh, Vasiliki Matzaraki, Rob Ter Horst, Gert Jan Scheffer, Leo A B Joosten, Mihai G Netea, Anaisa V Ferreira","doi":"10.1093/jleuko/qiaf123","DOIUrl":"10.1093/jleuko/qiaf123","url":null,"abstract":"<p><p>Trained immunity amplifies innate immune responses in an antigen-independent manner. This study explored the ability of trained human primary macrophages to modulate the phenotype and function of T cells. Macrophages play an important role in antigen presentation, resulting in T-cell activation and antigen-specific clonal expansion; however, few studies have investigated whether trained immunity induction in macrophages modulates T-cell activation. Here, through surface marker analysis of naive, β-glucan-, and Bacillus Calmette-Guérin-trained macrophages, we identified 8 distinct macrophage clusters following trained immunity induction. One of these populations showed an increase in surface activation markers CD40 and CD86, as well as major histocompatibility complex molecules. In vitro co-culture of T cells with autologous Bacillus Calmette-Guérin-trained macrophages resulted in a skewing toward TH17 cells. We also observed an increase in TH17 percentage after Bacillus Calmette-Guérin vaccination of human subjects. The bias toward TH17 triggered by trained macrophages required direct T cell to macrophage contact. Trained macrophages potentiated TH17 skewing independently of the antigen presented. While co-cultures of T cells and Bacillus Calmette-Guérin-trained macrophages responded with higher production of interferon-γ and interleukin-17 after stimulation, no clear shifts toward effector or memory T cells were observed. In conclusion, this study provides evidence that Bacillus Calmette-Guérin-trained macrophages can modulate T-cell function toward a TH17 phenotype, suggesting that Bacillus Calmette-Guérin-induced trained immunity has the potential to enhance not only innate immune responses but also to modify adaptive T-cell immunity.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryan J Collinson, Matthew D Linden, Kathryn A Fuller, Lynne Wilson, Bob Mirzai, Darren Boey, Zi Y Ng, Hun S Chuah, Jacques A J Malherbe, Rebecca Howman, Michael F Leahy, M Hasib Sidiqi, Janine H Collins, Willem H Ouwehand, Wendy N Erber, Belinda B Guo
{"title":"Megakaryocyte emperipolesis in myeloproliferative neoplasms: Are neutrophils friends or foes?","authors":"Ryan J Collinson, Matthew D Linden, Kathryn A Fuller, Lynne Wilson, Bob Mirzai, Darren Boey, Zi Y Ng, Hun S Chuah, Jacques A J Malherbe, Rebecca Howman, Michael F Leahy, M Hasib Sidiqi, Janine H Collins, Willem H Ouwehand, Wendy N Erber, Belinda B Guo","doi":"10.1093/jleuko/qiaf093","DOIUrl":"10.1093/jleuko/qiaf093","url":null,"abstract":"<p><p>Megakaryocyte emperipolesis is a biological process in which a cell penetrates and exists as a viable intact cell within another. It is a recognized morphological feature of myeloproliferative neoplasms (MPNs), in which neutrophils can be seen within megakaryocytes in bone marrow smears and sections. We aimed to determine whether neutrophil contents, specifically protein and RNA, are deposited within megakaryocytes due to emperipolesis. Evaluation of hematoxylin and eosin-stained bone marrow showed that 84% of MPN patients (n = 163) had megakaryocyte emperipolesis, most notably in enlarged megakaryocytes and those with pyknotic/condensed nuclei. Morphological assessment and immunohistochemical staining for CD15-neutrophil membrane antigen confirmed that majority of intramegakaryocytic cells were neutrophils, and that emperipolesis was more frequent in myelofibrosis patients and patients with pathologic reticulin. Furthermore, megakaryocytes in MPNs were observed to have intracellular positivity for neutrophil azurophilic granule protein myeloperoxidase (MPO) (n = 21 MPN patients) and specific granule lactoferrin (n = 56). Platelets were also used as a surrogate to establish if neutrophil contents had been transferred into megakaryocytes intracellularly of MPN patients, using mass spectrometry to assess protein and transcriptomic next-generation sequencing to assess messenger RNA (mRNA). A total of 109 neutrophil mRNA transcripts and 20 neutrophil granule proteins were upregulated in platelets of MPN patients compared with control subjects, including cathepsin-G and lactoferrin, with 5.1- and 4.6-fold increase in mRNA and 1.8- and 1.4-fold protein increases, respectively. This suggests that the transfer of neutrophil material occurs during emperipolesis in disease state, which could be a consequence of neutrophil degranulation or apoptosis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stepan Vodopyanov, Leslie Gunther-Cummins, Joseph Churaman, Xheni Nishku, Theofilos Poutahidis, Alexandros Hardas, Frank P Macaluso, George S Karagiannis
{"title":"Mapping murine thymic epithelial cells: functional ultrastructure and implications for thymopoiesis.","authors":"Stepan Vodopyanov, Leslie Gunther-Cummins, Joseph Churaman, Xheni Nishku, Theofilos Poutahidis, Alexandros Hardas, Frank P Macaluso, George S Karagiannis","doi":"10.1093/jleuko/qiaf115","DOIUrl":"https://doi.org/10.1093/jleuko/qiaf115","url":null,"abstract":"<p><p>We present a novel classification system for murine thymic epithelial cells (TECs), identifying 11 distinct types, four in the thymic cortex and seven in the medulla, based on their spatial localization and unique ultrastructural features. As key stromal components of the thymic microenvironment, TECs play indispensable roles in T cell development, including thymocyte selection, antigen presentation, and structural support. Our classification spans from the subcapsular cortex to the deep medulla and incorporates microanatomical context, morphology, and functional characteristics, providing a comprehensive and flexible framework to study TEC heterogeneity in relation to thymopoiesis. Aligning with TEC classification in rats and humans, this system highlights conserved spatial organization across species while remaining adaptable for refinement. Each TEC type is distinguished by features such as chromatin organization, cytoplasmic morphology, vacuolar content, and organelle distribution, attributes that suggest distinct functional contributions to various stages of thymocyte maturation. Importantly, the classification is designed for logical expansion both horizontally (inclusion of additional subtypes within the proposed TEC types) and vertically (inclusion of entirely novel TEC types). By integrating detailed morphological observations with testable functional hypotheses, this framework underscores the essential role of TEC diversity in supporting thymic architecture and orchestrating effective T cell output. Overall, it offers a robust foundation for future research into immune development and the pathological consequences of thymic dysfunction.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"117 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Rizakou, Annabelle Rosa, Lukas Johannes Weiss, Ecem T Sakalli, Giuseppe Rizzo, Philipp Burkard, Panagiota Arampatzi, Sarah Beck, Shanice Gundel, Kimberly Klapproth, Sourish Reddy Bandi, Marie Piollet, Vanessa Göb, Harald Schulze, David Stegner, Alma Zernecke, Bernhard Nieswandt, Clement Cochain
{"title":"Platelets drive macrophage inflammatory activation in vitro.","authors":"Anna Rizakou, Annabelle Rosa, Lukas Johannes Weiss, Ecem T Sakalli, Giuseppe Rizzo, Philipp Burkard, Panagiota Arampatzi, Sarah Beck, Shanice Gundel, Kimberly Klapproth, Sourish Reddy Bandi, Marie Piollet, Vanessa Göb, Harald Schulze, David Stegner, Alma Zernecke, Bernhard Nieswandt, Clement Cochain","doi":"10.1093/jleuko/qiaf114","DOIUrl":"10.1093/jleuko/qiaf114","url":null,"abstract":"<p><p>Macrophages have a dual role in tissue healing after injury as they perform tissue repair functions but can also precipitate tissue damage or promote fibrosis. Platelets, beyond their role in thrombosis and hemostasis, are crucial mediators of inflammation and interact with macrophages. Platelet-macrophage interactions have been proposed to modulate macrophage phenotype, including their profibrotic functions, but the full extent of the platelet impact on the macrophage transcriptome is unknown. Here, we aimed to investigate how platelets affect macrophage activation in vitro. Using experimental myocardial infarction (MI) in mice as a model of sterile tissue injury, we readily visualized the direct interaction of platelets with macrophages in the ischemic heart using fluorescence microscopy. Bulk RNA-sequencing of mouse bone marrow-derived macrophages co-cultured in vitro with thrombin-activated platelets showed a widespread proinflammatory activation, with upregulation of genes associated with inflammation (Il1b, Trem1, Tlr2, Cd14), angiogenesis (Vegfa) and response to hypoxia (Hif1a). Resting platelets also led to activation of inflammatory gene expression by macrophages, albeit to a much lesser extent. Activated or resting platelets, or the platelet-derived chemokine CXCL4, had a limited impact on macrophage expression of profibrotic genes (Spp1, Fn1). Using a transwell assay, we further demonstrate that the proinflammatory effects of platelets on the macrophage transcriptome were largely contact dependent. Altogether, our work shows that platelets interact with macrophages in the ischemic heart and polarize macrophages towards a proinflammatory phenotype in vitro, with potential implications for cardiac macrophage inflammatory activation after acute experimental MI.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}