Journal of Leukocyte Biology最新文献_第3页

The miniaturized isolation of neutrophil granules (MING) method allowed a deep proteome mapping of human neutrophil granules. 中性粒细胞颗粒微型化分离（MING）方法可对人类中性粒细胞颗粒进行深度蛋白质组图谱绘制。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae224

Gabrielly Alexandria, Hellen P Valerio, Mariana P Massafera, Lorenna R Reis, Fernando R Coelho, Paolo Di Mascio, Graziella E Ronsein

{"title":"The miniaturized isolation of neutrophil granules (MING) method allowed a deep proteome mapping of human neutrophil granules.","authors":"Gabrielly Alexandria, Hellen P Valerio, Mariana P Massafera, Lorenna R Reis, Fernando R Coelho, Paolo Di Mascio, Graziella E Ronsein","doi":"10.1093/jleuko/qiae224","DOIUrl":"10.1093/jleuko/qiae224","url":null,"abstract":"Neutrophils are the innate immune system's first line of defense, and their storage organelles are essential to their function. The storage organelles are divided into 3 different granule types named azurophilic, specific, and gelatinase granules, besides a fourth component called secretory vesicles. The isolation of neutrophil's granules is challenging, and the existing procedures rely on large sample volumes, about 400 mL of peripheral blood, precluding the use of multiple biological and technical replicates. Therefore, the aim of this study was to develop a miniaturized isolation of neutrophil granules method, using biochemical assays, mass spectrometry-based proteomics and a machine learning approach to investigate the protein content of these organelles. Neutrophils were isolated from 40 mL of blood collected from 3 apparently healthy volunteers and disrupted using nitrogen cavitation; the organelles were fractionated with a discontinuous 3-layer Percoll density gradient. The method was proven successful and allowed for a reasonable separation and enrichment of neutrophil's storage organelles using a gradient approximately 37 times smaller than the methods described in the literature. Moreover, mass spectrometry-based proteomics identified 368 proteins in at least 3 of the 5 analyzed samples, and using a machine learning strategy aligned with markers from the literature, the localization of 50 proteins was predicted with confidence. When using markers determined within our dataset by a clusterization tool, the localization of 348 proteins was confidently determined. Importantly, this study was the first to investigate the proteome of neutrophil granules using technical and biological replicates, creating a reliable database for further studies.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391101","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}

引用次数: 0

The protective role of transcription factor Nrf2 in murine macrophage activation syndrome. 转录因子 Nrf2 在小鼠巨噬细胞活化综合征中的保护作用

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae225

Paul M Gallo, Em Elliott, Grace C Ford, Chhanda Biswas, Jadyn M Wheaton, Jihwan Kim, Connie L Jiang, Niansheng Chu, Portia A Kreiger, Michele P Lambert, Edward M Behrens

{"title":"The protective role of transcription factor Nrf2 in murine macrophage activation syndrome.","authors":"Paul M Gallo, Em Elliott, Grace C Ford, Chhanda Biswas, Jadyn M Wheaton, Jihwan Kim, Connie L Jiang, Niansheng Chu, Portia A Kreiger, Michele P Lambert, Edward M Behrens","doi":"10.1093/jleuko/qiae225","DOIUrl":"10.1093/jleuko/qiae225","url":null,"abstract":"Objective: Macrophage activation syndrome (MAS) is characterized by multilineage cytopenias, hypercytokinemia, and tissue hemophagocytosis. Transcription factor Nrf2 is a master regulator of redox homeostasis. In this work, we aim to investigate the role of Nrf2 in murine hyperinflammation and the mechanisms by which Nrf2 activation by red blood cell products regulates proinflammatory cytokine production.Methods: We induced murine MAS in wild-type and Nrf2 knockout (Nrf2-/-) mice by repeat administration of TLR9-agonist CpG. Clinical and biochemical markers of disease were measured including complete blood counts, liver and spleen pathology, serum free heme, ferritin, and cytokine profiles. In vitro bone marrow-derived macrophages and dendritic cells were used to investigate regulation of CpG-induced cytokine expression by oxidized red blood cells and hemin.Results: Patients with hyperinflammatory disease had higher levels of Nrf2 gene expression. Mice with CpG-induced hyperinflammation had elevated systemic lipid peroxidation, which was exacerbated in Nrf2-/- mice. Compared with wild-type control mice, Nrf2-/- mice developed significantly worse organomegaly, organ pathology, and reticulocytosis. Nrf2-/- mice had exacerbated hypercytokinemia in cytokines central MAS physiology: interleukin (IL)-12, interferon γ, and IL-10. In vitro, we found that oxidized red blood cell lysates and hemin were able to suppress IL-12 transcription and protein production from bone marrow-derived dendritic cells in an Nrf2-dependent manner.Conclusion: Together, our findings show that transcription factor Nrf2 is highly expressed in patients with hyperinflammatory disease and demonstrate a protective role for Nrf2 in a murine model of MAS in part due to Nrf2-mediated suppression of proinflammatory cytokine production.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400494","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}

引用次数: 0

CD56 does not contribute to the antitumor, tissue homing, and glycolytic capacity of human NK cells. CD56 对人类 NK 细胞的抗肿瘤、组织归巢和糖酵解能力没有贡献。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae227

Ana L Portillo, Eduardo A Rojas, Misaal Mehboob, Adnan Moinuddin, Elizabeth Balint, Emily Feng, Christopher Silvestri, Fatemeh Vahedi, Tyrah M Ritchie, Alexa J Mansour, Jonathan L Bramson, Ali A Ashkar

{"title":"CD56 does not contribute to the antitumor, tissue homing, and glycolytic capacity of human NK cells.","authors":"Ana L Portillo, Eduardo A Rojas, Misaal Mehboob, Adnan Moinuddin, Elizabeth Balint, Emily Feng, Christopher Silvestri, Fatemeh Vahedi, Tyrah M Ritchie, Alexa J Mansour, Jonathan L Bramson, Ali A Ashkar","doi":"10.1093/jleuko/qiae227","DOIUrl":"10.1093/jleuko/qiae227","url":null,"abstract":"Natural killer (NK) cells are critical innate immune cells involved in the clearance of virally infected and malignant cells. Human NK cells are distinguished by their surface expression of CD56 and a lack of CD3. While CD56 expression and cell surface density has long been used as the prototypic marker to characterize primary human NK cell functional subsets, the exact functional role of CD56 in primary human NK cells is still not fully understood. Here, we eliminated the expression of CD56 in human ex vivo expanded NK cells (CD56bright) using CRISPR/Cas9 in order to assess the function of CD56 in this highly activated and cytotoxic NK cell population. We show that the expression of CD56 has no effect on NK cell proliferative capacity or expression of various activation and inhibitory markers. Further, CD56 does not contribute to NK cell-mediated cytotoxicity, inflammatory cytokine production, or the ability of NK cells to control tumor engraftment in vivo. We also found that while deletion of CD56 did not impact NK cell glycolytic metabolism, it did increase NK cell reliance on oxidative phosphorylation. Last, CD56 does not alter expanded NK cell in vivo tissue trafficking. Our results indicate that while CD56 expression could be used to indicate a hyperfunctional state of NK cells, it does not directly influence the antitumor functions of expanded NK cells.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502158","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}

引用次数: 0

Reversible role of MIR654/3P and MIR9/3P in pathogenesis of Epstein-Barr virus-negative, but not Epstein-Barr virus-positive, Burkitt lymphoma. MIR654/3P 和 MIR9/3P 在 Epstein-Barr 病毒阴性而非阳性伯基特淋巴瘤发病机制中的可逆作用。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae237

Yu Gong, Wenhua Fu

{"title":"Reversible role of MIR654/3P and MIR9/3P in pathogenesis of Epstein-Barr virus-negative, but not Epstein-Barr virus-positive, Burkitt lymphoma.","authors":"Yu Gong, Wenhua Fu","doi":"10.1093/jleuko/qiae237","DOIUrl":"10.1093/jleuko/qiae237","url":null,"abstract":"The role of MIR654 in Burkitt lymphoma (BL) and whether it impacts expression of MYC and its downstream activated MIR9 is not known. Expression of MYC, MYCN, MYCL, MIR9/3P, MIR654/5P, and MIR654/3P was assessed by quantitative reverse-transcription polymerase chain reaction in biopsy samples from Epstein-Barr virus-negative (EBV-) and EBV+ BL patients and BL cell lines. Effects of modulation of MIR9/3P and MIR654/3P on cell proliferation, apoptosis, and chemosensitivity were evaluated. Luciferase reporter assay was performed to validate the putative target of MIR654/5P. Effects of MIR9/3P and MIR654/3P on tumor burden and disease outcome were evaluated using xenograft model of BL. Expression of MYC, MYCN, and MIR9/3P was higher in all BL patient samples and cell lines. Expression of MIR654/3P was downregulated in EBV- BL patient samples and cell lines compared with either noncancer lymphoid-reactive hyperplasia or EBV+ samples and cell lines. Additionally, MIR654/3P overexpression inhibited cell proliferation, induced apoptosis, and increased chemosensitivity in EBV- BL cell lines. Luciferase reporter assay confirmed that MYC is a target of MIR654/3P in both EBV- and EBV+ BL cell lines; however, the effect of MIR654/3P-mediated targeting of MYC is overridden in EBV+ cells. Administration of MIR654/3P mimic or MIR9/3P antagomir in the xenograft model decreased tumor burden and increased survival. Combined intervention with MIR654/3P mimic and MIR9/3P antagomir had synergistic action on decreasing tumor burden and improving disease outcome. MIR654/3P, as a putative tumor suppressor in EBV- BL, collaborating with MIR9/3P might serve as a therapeutic agent to treat EBV- BL patients in combination with existing chemotherapy and immunotherapy regimes.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502163","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}

引用次数: 0

Resveratrol potentiates BCG-induced trained immunity in human monocytes. 白藜芦醇能增强卡介苗诱导的人类单核细胞训练免疫力

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae241

Ozlem Bulut, Ilayda Baydemir, Gizem Kilic, Jorge Domínguez-Andrés, Mihai G Netea

{"title":"Resveratrol potentiates BCG-induced trained immunity in human monocytes.","authors":"Ozlem Bulut, Ilayda Baydemir, Gizem Kilic, Jorge Domínguez-Andrés, Mihai G Netea","doi":"10.1093/jleuko/qiae241","DOIUrl":"10.1093/jleuko/qiae241","url":null,"abstract":"Resveratrol is a natural polyphenol derived from plants such as grapes and berries. In addition to its role in plants during injury and infection, various cardioprotective, neuroprotective, and longevity-promoting effects were reported in diverse model organisms. The primary target of resveratrol is the deacetylase Sirtuin 1, which regulates many immunological processes, including BCG-induced trained immunity response in humans. We, therefore, investigated the effect of resveratrol on trained immunity induced by BCG, β-glucan (BG), Candida albicans, or oxidized low-density lipoprotein (oxLDL). Using an in vitro model of trained immunity with monocytes obtained from healthy donors, we demonstrate that resveratrol amplifies BCG-induced trained immunity regarding IL-6 and TNFα production after a secondary challenge. Although resveratrol did not improve and even limited glycolysis, oxidative phosphorylation, and reactive oxygen species production, it enhanced the permissive epigenetic mark H3K27Ac on IL-6 and TNFα promoters. In contrast to BCG-induced trained immunity, resveratrol potently inhibited training induced by BG, C. albicans, oxLDL, and muramyl dipeptide, a peptidoglycan component of BCG. Resveratrol's unique boosting effect on BCG training depended on BCG being alive and metabolically active. These results suggest that resveratrol might amplify the effects of BCG vaccination, which should be mechanistically characterized further. In addition, resveratrol could alleviate oxLDL-induced training of innate immune cells in atherosclerosis, and in vivo studies of trained immunity combined with resveratrol are warranted to explore these therapeutic possibilities.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568802","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}

引用次数: 0

STING coordinates resolution of inflammation during wound repair by modulating macrophage trafficking through STAT3. STING 通过 STAT3 调节巨噬细胞的迁移，在伤口修复过程中协调炎症的消解。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae175

Cheng Chen, Xin Cai, Zhihui Liu, Weiguang Zhang, Jiacai Yang, Yuanyang Tang, Yunxia Chen, Yong Huang, Wengang Hu, Xiaorong Zhang, Junyi Zhou, Yanjun Wu, Wenjing Yin, Ruoyu Shang, Qudong Lu, Hao Sheng, Zhenyu Ju, Gaoxing Luo, Weifeng He

{"title":"STING coordinates resolution of inflammation during wound repair by modulating macrophage trafficking through STAT3.","authors":"Cheng Chen, Xin Cai, Zhihui Liu, Weiguang Zhang, Jiacai Yang, Yuanyang Tang, Yunxia Chen, Yong Huang, Wengang Hu, Xiaorong Zhang, Junyi Zhou, Yanjun Wu, Wenjing Yin, Ruoyu Shang, Qudong Lu, Hao Sheng, Zhenyu Ju, Gaoxing Luo, Weifeng He","doi":"10.1093/jleuko/qiae175","DOIUrl":"10.1093/jleuko/qiae175","url":null,"abstract":"Efficient cutaneous wound healing requires a coordinated transition between inflammatory phases mediated by dynamic changes in leukocyte subset populations. Here, we identify STING as a key innate immune mediator governing timely resolution of inflammation by regulating macrophage dynamics during skin repair. Using a mouse model, we show STING deficiency caused delayed wound closure associated with abnormal persistence of TNF-α+ leukocytes. This resulted from the impaired macrophage recruitment. STING controlled the trafficking of bone marrow myeloid cells into blood and wounds, intrinsically enhancing macrophage migratory capacity through STAT3 activation. Specifically, STING modulated the production of monocyte chemokines and their receptors CCR2/CCR5 to enable efficient egress and wound infiltration. Consequently, disrupted systemic and local STING-STAT3-chemokine signaling combine to delay macrophage influx. This study elucidates STING as a critical rheostat tuning macrophage responses through STAT3 to orchestrate inflammatory resolution necessary for efficient wound healing. Our findings have broad implications for targeting STING therapeutically in both regenerative medicine and inflammatory disease contexts.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906735","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}

引用次数: 0

Intracellular methylglyoxal accumulation in classically activated mouse macrophages is mediated by HIF-1α. 经典活化小鼠巨噬细胞内甲基乙二酸的积累由 HIF-1α 介导

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae215

Daniel Prantner, Stefanie N Vogel

{"title":"Intracellular methylglyoxal accumulation in classically activated mouse macrophages is mediated by HIF-1α.","authors":"Daniel Prantner, Stefanie N Vogel","doi":"10.1093/jleuko/qiae215","DOIUrl":"10.1093/jleuko/qiae215","url":null,"abstract":"Approximately one million cases of sepsis in the United States occur annually. The early phase of sepsis features dramatic changes in host metabolism and inflammation. While examining the effects of metabolic pathways on inflammation, we discovered that the highly reactive glycolytic metabolite, methylglyoxal (MG), accumulates intracellularly during classical activation of macrophages. Herein, we explored the role of glycolysis and the master regulator of glycolysis, Hypoxia-Inducing Factor-1α (HIF-1α), in inflammation and MG accumulation in mouse and human macrophages. To determine how HIF-1α regulates the inflammatory response of macrophages, we correlated HIF-1α stabilization with proinflammatory gene expression and MG-adduct accumulation in WT vs HIF1a-deficient macrophages treated with LPS or LPS + IFN-γ. A nearly complete loss of HIF-1α protein expression in response to the hypoxia mimetic, cobalt chloride, confirmed the phenotype of the HIF1a-deficient macrophages. Moreover, absence of HIF-1α was also associated with decreased MG accumulation. Increasing the glucose concentration in cultured macrophages was sufficient to cause accumulation of endogenous MG-adducts which correlated with increased Tnf and Il1b expression during classical activation. The use of the MG antagonist, aminoguanidine, led to a significant decrease in Tnf and Il1b expression in both mouse macrophages and the THP-1 human macrophage cell line. Although off-target effects cannot be ruled out, these results are consistent with the possibility that MG regulates cytokine expression in classically activated macrophages. Collectively, this work suggests that HIF-1α stabilization is upstream of MG accumulation and that targeting the activity of HIF-1α in macrophages may be therapeutic during sepsis by limiting endogenous MG accumulation.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365525","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}

引用次数: 0

Characteristics of the IgM repertoires in the peripheral blood of early rheumatoid arthritis patients. 早期类风湿关节炎患者外周血中 IgM 复合物的特征

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae236

Binbin Hong, Qiulan Li, Qiaoling Liu, Rongfu Huang, Mei'er Wang, Ziyue Guo, Jiewei Huang, Jiaqi Wang, Chunmei Fan, Tianlei Ying

{"title":"Characteristics of the IgM repertoires in the peripheral blood of early rheumatoid arthritis patients.","authors":"Binbin Hong, Qiulan Li, Qiaoling Liu, Rongfu Huang, Mei'er Wang, Ziyue Guo, Jiewei Huang, Jiaqi Wang, Chunmei Fan, Tianlei Ying","doi":"10.1093/jleuko/qiae236","DOIUrl":"10.1093/jleuko/qiae236","url":null,"abstract":"Rheumatoid arthritis is a common autoimmune disease, but little is known about the characteristics of the B cell repertoires in the peripheral blood. In this study, the peripheral IgM repertoires of early rheumatoid arthritis (ERA) patients were analyzed by high-throughput sequencing and bioinformatics analyses. Clonal expansion was observed in IgM repertoires of ERA patients. Interestingly, a subset of the dominant clones in ERA repertoires showed self- and polyreactivity to several autoantigens. The clones were also identified in IgM repertoires of healthy adults but they were not expanded, suggesting that they may originate from the natural autoreactive B cell repertoire. Additionally, the ERA repertoires exhibited a greater extent of somatic hypermutations, particularly in the ERA dominant clones, resulting in an enrichment of amino acids important for antigen-antibody interaction. The in-depth analysis of B cell repertoires improved our knowledge of the IgM repertoires in ERA, offering potential insights into the disease's pathogenesis.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502159","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}

引用次数: 0

Unveiling the role of resident memory T cells in psoriasis. 揭示驻留记忆T细胞在银屑病中的作用。

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae254

Juan Saavedra-Almarza, Felipe Malgue, Moira García-Gómez, Solange Gouët, Natalie Edwards, Verónica Palma, Mario Rosemblatt, Daniela Sauma

引用次数: 0

Basophils induce protumorigenic cytokines from A549 lung adenocarcinoma via mechanisms requiring IgE, galectin-3, and IL-3 priming. 嗜碱性粒细胞通过需要 IgE、Galectin-3 和 IL-3 引物的机制诱导 A549 肺腺癌产生促肿瘤细胞因子

IF 3.6 3区医学

Journal of Leukocyte Biology Pub Date : 2025-03-14 DOI: 10.1093/jleuko/qiae233

John T Schroeder, Laurent Ehrlich, Anja P Bieneman

{"title":"Basophils induce protumorigenic cytokines from A549 lung adenocarcinoma via mechanisms requiring IgE, galectin-3, and IL-3 priming.","authors":"John T Schroeder, Laurent Ehrlich, Anja P Bieneman","doi":"10.1093/jleuko/qiae233","DOIUrl":"10.1093/jleuko/qiae233","url":null,"abstract":"Galectin-3 (Gal-3) is implicated in innate immune cell activation in a host of diseases/conditions. We identified a unique response whereby human basophils secrete interleukin (IL)-4/IL-13 when cocultured with A549 cells-lung adenocarcinoma. While displaying parameters consistent with standard IgE-dependent activation, these Gal-3-dependent responses occurred in the absence of specific IgE/allergens and required cell-to-cell contact. We now hypothesize that this mode of activation also impacts A549 function. Our findings show that cytokines are induced in basophil/A549 cocultures that are not detected when either cell is cultured alone, in particular IL-6. As previously shown for IL-4/IL-13, IL-6 production also required cell-to-cell contact and was dependent on A549-Gal-3, as clones deficient of this lectin induced less cytokine. Using culture-derived basophils (CDBAs), we demonstrate that the IL-6 response and production of another tumorigenic factor, vascular endothelial growth factor A (VEGF-A), are induced in CDBA/A549 cocultures but only after passively sensitizing CDBAs with IgE, in a manner similar to IL-4/IL-13. However, IgE-dependent activation of basophils/CDBAs cultured alone failed to induce IL-6/VEGF. Importantly, IL-3-primed basophils, even those fixed with paraformaldehyde, readily induced IL-6/VEGF-A in cocultures, thus verifying that these cytokines are derived from A549. Overall, these results suggest a complex mechanism whereby Gal-3/IgE interactions between IL-3-primed basophils and A549 have the potential to modulate cytokine production by both cells. With Gal-3 implicated not only in many diseases ranging from asthma to cancer, but also in normal physiological conditions, such as wound healing, these findings are predicted to provide insight into the molecular mechanisms by which this lectin (and IgE) functions in these processes.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467619","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}

引用次数: 0