ACS Nano
·
2024
·
IF 15.8
Weiya Zeng,Ying Wang,Qing Zhang,Chengyi Hu,Jing Li,Jinwei Feng,Chenglu Hu,Yong Su,Jie Lou,Ling Long,Xing Zhou
Cancer metastasis is the main cause of cancer-related deaths and involves the interaction between tumor cells and neutrophils. In this study, we developed activated neutrophil membrane-coated nanoparticles (aNEM NPs) as nanodecoys to block neutrophil-mediated cancer metastasis. The aNEM NPs were fabricated by cloaking poly(lactic acid) nanoparticles with membranes derived from activated neutrophils and inherited the functional proteins of activated neutrophils. We demonstrated that aNEM NPs could interfere with the recruitment of neutrophils to the primary tumor and premetastatic niches, inhibit the adhesion of neutrophils to tumor vascular endothelium and circulating tumor cells (CTCs), and disrupt the formation of CTC–neutrophil clusters in vitro and in vivo. In 4T1-bearing mice, aNEM NPs could effectively reduce breast cancer metastasis to various organs in mice. Our results suggest that aNEM NPs are a promising nanomedicine for preventing or treating cancer metastasis by acting as neutrophil nanodecoys.
研究领域:
肿瘤学
·
纳米医学
·
生物医学工程
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Communications Biology
·
2025
·Vol. 8
·期 1
·1-15
·
IF 5.1
Fan Zhan,Xu Yilun,Lu Yafang,Li Xinlin,Xu Mengli,Liu Jinxin,Cai Zhenzhen,Liu Jiayang,Su Jingping,Wang Jialu,Luo Qingming,Zhang Zhihong,Liu Zheng
The excessive accumulation of neutrophils within the epidermis is a significant hallmark of cutaneous diseases; however, the mechanisms governing neutrophil transepidermal migration (NTEM) remain inadequately understood. In this study, we develop trichromatic-fluorescence-labeled chimeric mice by utilizing Cx3cr1 GFP/+ Lyz2 RFP/+ mice as bone marrow donors and Krt14 YFP/+ mice as recipients. This approach enables us to visualize the process of NTEM and the crosstalk between neutrophils and monocytes in a murine model of irritant contact dermatitis (ICD). Intravital imaging reveals a preferential transmigration of neutrophils through hair follicle (HF), where dermal neutrophils exhibit limited mobility and interact with dermal monocytes. Notably, 18 h following hapten exposure, dermal neutrophils continuously migrate toward HF regions and form clusters within 3 h. Importantly, MMP-9 is identified as essential for the NTEM process; the depletion of dermal monocytes results in a significant reduction of MMP-9 expression in the skin and inhibits the NTEM process in ICD. Mechanistically, dermal monocytes are found to be a crucial source of the cytokines TNF-α and CXCL2, which promote the upregulation of MMP-9 in neutrophils. Therefore, our results highlight HF regions as crucial gateways for dermal monocyte-modulated NTEM and provide visual insights into the crosstalk between neutrophils and monocytes in inflammatory skin disorders.
研究领域:
免疫学
·
皮肤病学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2025
·Vol. 20
·期 1
·1-18
·
IF 5.7
Wang Xu,Peng Hui-Ming,Zhang Meng-Ru,Li Jing-Jing,Zhao Chuan-Peng,Zhang Ya-Li,Wang Si-Yu,Zhu Si-Ying,Lu Jian-Kang,Yin Hai-Long,Yin Qiang,Fang Jin-Bo
Background Steroid-resistant asthma (SRA) is a form of asthma resistant to corticosteroid therapy, which is characterized by the presence of neutrophil-predominant inflammatory response and neutrophil extracellular traps (NETs) formation. Hyssopus cuspidatus Boriss., a traditional Uyghur medicine, is known for its efficacy in treating inflammatory lung conditions such as asthma. However, the therapeutic impact and underlying mechanisms of Hyssopus cuspidatus Boriss.’s volatile oil (HVO) in SRA have not been fully elucidated. Methods This study established an ovalbumin/lipopolysaccharide (OVA/LPS)-induced SRA mice model to evaluate the therapeutic effect of HVO on SRA. UPLC-QE-Orbitrap-MS was applied to analyze the serum compositions of HVO. Network pharmacology and molecular docking were employed to uncover the complex mechanisms of HVO in treating SRA and predict potential effective compounds in HVO. Furthermore, in vivo studies in SRA mice and in vitro studies using HL-60 cells and bone marrow neutrophils were conducted to validate the mechanism. Results HVO could significantly ameliorate OVA/LPS-induced SRA symptoms, including airway hyperresponsiveness, airway inflammation, mucus overproduction and airway remodeling. 41 prototype compounds, 65 Phase I metabolites and 50 Phase II metabolites were identified in serum-containing HVO. The integration of network pharmacology with experimental validation revealed that HVO can inhibit the formation of NETs by targeting neutrophil elastase, thereby exerting a therapeutic influence on SRA. Meanwhile, molecular docking results showed that 3-methoxy-4-hydroxy mandelonitrile, 1,2,3,4-tetrahydro-1,5,7-trimethyl-naphthalene, cis-calamenene and aristol-1(10)-en-9-yl isovalerate may be the therapeutic compounds of HVO in treating SRA. Conclusion These findings suggest that HVO is a promising therapeutic candidate for neutrophil-dominant SRA by targeting NETs formation.
研究领域:
药理学
·
免疫学
·
呼吸病学
·
传统医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Sui Dezhi,Song Yanzhi,Deng Yihui
Neutrophils play a critical role in the cancer-immunity cycle and are associated with poor clinical outcomes. Recent research has primarily focused on the targeted delivery, phenotypic reversal, and reprogramming of tumor-associated neutrophils, while the impact of disease-associated neutrophils (DANs) on antitumor therapy remains understudied. Since liposomes, as drug delivery carriers, possess excellent biocompatibility and stability, making them particularly suitable for combination therapy, we optimized the formulation of asymmetrically branched polyethylene glycol-modified mitomycin C lipid prodrug liposomes (PEG2,5 K@MLP-L) and prepared hyaluronic acid and sialic acid ester stearate-co-modified dexamethasone palmitate liposomes (HA*SAS@DXP-L) to study DANs in normal, obese, aged, and septic mice. An increase in mitochondria and lysosomes in Ly-6G+CXCR2high DANs accelerated drug clearance, reduced CD3+CD8+ T cell activity in tumor-draining lymph nodes, and decreased CD8+ T cell infiltration in tumors. As the proportion of DANs increased, the efficacy of PEG2,5 K@MLP-L decreased. Combination therapy with PEG2,5 K@MLP-L and HA*SAS@DXP-L can reshape DANs, promote the cancer-immunity cycle, and enhance treatment efficacy. This study identifies key characteristics and functions of DANs and presents a promising strategy for improving clinical outcomes.Graphical
研究领域:
肿瘤学
·
免疫学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Shuai Dong,Xingyuan Bai,Bin Chen,Minzhe Fan,Qi Liu,Yubo Zhao,Linsen Li*,Dan Zhu
Background: Panzerina lanata (Lanata) is generally used to treat pustule infection in Inner Mongolia folk medicine and is called “the holy medicine for pustule.” However, the pharmacological mechanism of Lanata in treating pustule infection is still unclear.Aims: This study aimed to investigate the therapeutic effects of Lanata on skin infection and explore the underlying mechanisms.Methods: A skin wound methicillin-resistant Staphylococcus aureus (MRSA) infection mouse model was established to evaluate the healing effect of Lanata on infected wounds. In vitro assays were also conducted to determine the antibacterial activity of Lanata. Flow cytometry and immunohistochemistry were used to dynamically detect the number of neutrophils in the bone marrow, peripheral blood, and MRSA-infected wound. Protein expression in the infected wound skin was detected by a protein chip. Using an air pouch MRSA infection mouse model, the number of neutrophils, reactive oxygen species (ROS) level in neutrophils, and neutrophil extracellular trap (NET) formation were dynamically detected by flow cytometry and immunofluorescence. RNA-seq, RT-qPCR, flow cytometry, ELISA, and CXC chemokine receptor 2 (CXCR2) and P-selectin glycoprotein ligand-1 (PSGL-1) inhibitors were used to explore the mechanism of Lanata in regulating neutrophils.Results: In vitro assays showed that Lanata had no direct antibacterial activity. In skin wound MRSA-infected mouse, Lanata promoted the rapid migration of neutrophils from the bone marrow via peripheral blood to the wound site to eradicate MRSA in the acute stage of infection and accelerate wound healing. Skin protein chip analysis showed that Lanata upregulated CXCR2 and PSGL-1 protein levels in skin wounds. Furthermore, analysis using the air pouch MRSA infection mouse model found that Lanata not only promoted the rapid migration of neutrophils from peripheral blood to the air pouch but also enhanced the activation of neutrophils, including the increase of ROS and the release of NETs, and upregulated the expression of CXCR2, PSGL-1, and myeloperoxidase (MPO) in neutrophils. Inhibition of CXCR2 and MPO significantly attenuated the effect of Lanata on promoting migration and activation of neutrophils.Conclusion: Panzerina lanata resists MRSA infection by promoting migration and activation of neutrophils to rapidly eradicate MRSA.
研究领域:
药理学
·
免疫学
·
微生物学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT CANCER DRUG TARGETS
·
2024
·Vol. 25
·期 3
·294-305
·
IF 2.3
Yiping Zheng,Jianfeng Cai,Qiuhong Ji,Luanmei Liu,Kaijun Liao,Lie Dong,Jie Gao,Yinghui Huang
BackgroundLung cancer remains a major global health threat due to its complex microenvironment, particularly the role of neutrophils, which are crucial for tumor development and immune evasion mechanisms. This study aimed to delve into the impact of lung cancer cell-conditioned media on neutrophil functions and their potential implications for lung cancer progression.MethodsEmploying in vitro experimental models, this study has analyzed the effects of lung cancer cell-conditioned media on neutrophil IL-8 and IFN-γ secretion, apoptosis, PD-L1 expression, and T-cell proliferation by using techniques, such as ELISA, flow cytometry, immunofluorescence, and CFSE proliferation assay. The roles of IL-8/PD-L1 in regulating neutrophil functions were further explored using inhibitors for IL-8 and PD-L1.ResultsLung cancer cell lines were found to secrete higher levels of IL-8 compared to normal lung epithelial cells. The conditioned media from lung cancer cells significantly reduced apoptosis in neutrophils, increased PD-L1 expression, and suppressed T-cell proliferation and IFN-γ secretion. These effects were partially reversed in the presence of IL-8 inhibitors in Tumor Tissue Culture Supernatants (TTCS), while being further enhanced by IL-8. Both apoptosis and PD-L1 expression in neutrophils demonstrated dose-dependency to TTCS. Additionally, CFSE proliferation assay results further confirmed the inhibitory effect of lung cancer cell-conditioned media on T-cell proliferation.ConclusionThis study has revealed lung cancer cell-conditioned media to modulate neutrophil functions through regulating factors, such as IL-8, thereby affecting immune regulation and tumor progression in the lung cancer microenvironment.
研究领域:
肿瘤学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2025
·
IF 2.9
Xiaoyu Mao,Dashuang Mo,Yuqin Cheng,Mengzhu Lv
N -(1,3-Dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD), a commonly used antioxidant in tire manufacturing, has been widely detected in the environment and shown to exhibit acute toxicity in several organs. However, the effects of 6PPD on immune responses, particularly following injury, remain poorly understood. In this study, we investigated the impact of 6PPD exposure on immune responses using zebrafish as a model. 6PPD exposure disrupted caudal fin regeneration at various stages of the regenerative process. Further analysis revealed that 6PPD impaired immune responses following fin amputation, as evidenced by the reduced number of lyz + /mpx + neutrophils and the downregulation of key immune-related genes. Besides, the morphology of neutrophils was changed upon 6PPD exposure, indicating the defective migration of immune cells. The incubation of zebrafish larvae with lipopolysaccharide (LPS), which induces global immune responses, also exhibited impaired immune function when combined with 6PPD exposure. Additionally, the injection of LPS into the egg yolk or trunk exacerbated immune responses at the injury site, yet 6PPD exposure significantly reduced neutrophil accumulation and downregulated the expression of immune-related genes, confirming the toxicity of 6PPD in immune responses. These findings provide new insights into the toxic effects of 6PPD on immune responses during injury, highlighting its potential to impair immune function in animals and human.
研究领域:
毒理学
·
免疫学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INFLAMMATION
·
2024
·
IF 4.5
Yuan Xin,Sheng Liang,Shi Guang,Jiang Leiwei,Lian Chengxiang
Rosacea is a chronic facial inflammatory skin disease that occurs with dysfunction of the immune system. Colchicine was reported to have anti-inflammatory properties. However, the impact of colchicine on rosacea remains unclear. In the present study, the phenotype of rosacea lesions was evaluated by the redness score, inflammatory biomarkers were analyzed by reverse transcription PCR (RT‒PCR), and the infiltration of inflammatory cells was assessed by IHC analysis and immunofluorescence in a rosacea-like mouse model. In vitro , RT‒PCR was used to identify the inflammatory factors that Toll-like receptor 2 (TLR2) agonist caused neutrophils to produce, and immunofluorescence and coimmunoprecipitation were used to identify putative signalling pathways. We found that skin erythema and histopathological alterations, as well as elevated proinflammatory factors (IL-1β, IL-6, TNFα, CXCL2) and CAMP, were significantly ameliorated by colchicine treatment in LL37-induced rosacea-like mice. In addition, colchicine reduced the colocalization of TLR2 and neutrophils and the formation of neutrophil extracellular trap networks (NET) in mouse lesions. In neutrophils, colchicine markedly reduced TLR2 agonist-induced inflammatory biomarker expression, NET formation, and ROS production. Moreover, we found that LL37 could bind to TLR2 upon activation of TLR2 in neutrophils. Importantly, colchicine could repress the combination of TLR2 and LL37 in vivo . Finally, bioinformatics methods further validated the key molecules of neutrophil-related inflammation in rosacea, which is consistent with our experimental findings. Collectively, colchicine ameliorated rosacea-like dermatitis by regulating the neutrophil immune response activated by the TLR2 pathway, indicating that it could be an effective therapeutic option for patients with rosacea.
研究领域:
皮肤科
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Yingxin Long,Tingting Zhao,Yuan Xiao,Shang Kong,Ranjing Wang,Kexin Cai,Hong Nie
Sophora flavescens Ait. (SFA), an extensively utilized herb for the treatment of fevers, inflammatory disorders, ulcers and skin diseases related to bur, contains oxymatrine (OMT) as its principal active constituent. OMT exerts regulatory effects over inflammation, oxidative stress and apoptosis. Neutrophils, critical regulators of the inflammation response, have not been thoroughly elucidated regarding the protective properties and underlying mechanisms of OMT-mediated anti-inflammation. This study was aim to explore the protective effect of OMT on neutrophils under inflammatory conditions and delve into its potential mechanism. Leveraging the advantages of zebrafish, an animal model with a real-time dynamic observation system, we established an in vivo caudal fin wound model and a copper sulfate induced-inflammation model in zebrafish line Tg (mpx:GFP) . The result revealed that OMT significantly attenuated neutrophil migration, upregulated the mRNA expression levels of JNK, casp3, mapk14a, mapkapk2a and map2k1 damaged by zebrafish caudal fin wound model, and downregulated mRNA expression levels of JNK, casp3, mapk14a, mapkapk2a and map2k1 in the copper sulfate injury model. In vitro experiments demonstrated that OMT modulated the chemotaxis response of primary neutrophils from mice, enhanced phagocytosis, reduced oxidative stress and alleviated inflammation level. We hypothesize that the OMT may exert its anti-inflammatory effects by regulating primary neutrophils through the MAPK signaling pathway.
研究领域:
药理学
·
免疫学
·
分子生物学
·
斑马鱼研究
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
Rongrong Huang,Ranran Chen,Lijuan Xing,Lianhao Wu,Wenwen Zhu,Junsong Jing,Ting Zhou,Yueguo Wu,Sheng Zhang,Zhenqiang You
Background Viral pneumonia is the most common and lethal pandemic disease, but there are no broad-spectrum antiviral drugs with high genetic barriers to resistance. To elucidate the mechanisms of viral pneumonia progression and potential targets for its treatment. Methods Viral pneumonia models were induced by the PR8 virus strain in wild-type (WT) and STING knockout (STING-KO) mice. Series of molecular biology techniques were used to evaluate the severity of pneumonia and cytokine levels. Results In this study, STING (stimulator of interferon genes) was activated in the lungs of virus-infected mice, leading to cytokine production and amplification of the immune response, thereby causing rapid deterioration of symptoms. Furthermore, excessive activation of innate immune response via STING was prevented by a STING inhibitor (C-176), which significantly reduced viral lung inflammation. The formation of neutrophil extracellular traps (NETs) was similarly suppressed during viral pneumonia treatment with STING inhibitors (C-176), and NETs formation and STING expression were positively correlated, indicating that STING plays an important role in NETs formation. Symptoms of pneumonia in STING-KO mice infected with PR8 were significantly milder than those in WT mice, and NETs were less likely to form in the lung tissue of STING-KO mice. Additionally, transcriptomic analysis revealed that STING-mediated regulation of NETs may be associated with gasdermin D (GSDMD), and immunoprecipitation experiments revealed that STING, GSDMD, and NETs-related proteins interact with each other. Immunofluorescence assays revealed that in neutrophils from WT mice, STING and GSDMD were colocalized on the membrane after viral infection, whereas in neutrophils from STING-KO mice, GSDMD expression was decreased after exposure to the virus. Conclusions Our study demonstrated that targeted intervention with STING alleviated pneumonia by inhibiting inflammation and NETs formation. The study also revealed that blocking STING could inhibit the activation of GSDMD to inhibit NETs formation, slowing the progression of viral pneumonia.
研究领域:
免疫学
·
病毒学
·
分子生物学
·
呼吸病学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Shu-Zhen Dai,Ri-Hong Wu,Hengyu Chen,Ming-Hui Chen,Weijing Xie,Wu-Ping Zheng,Guang-Hong Tan,Feng-Ying Huang
Background The process of NETosis is observed in a range of inflammatory conditions. Progesterone (P4) has been shown to alleviate inflammation caused by viral infections such as influenza and SARS-CoV-2. However, the precise molecular mechanisms responsible for this effect are not yet fully understood. Therefore, the present investigation aims to explore whether P4 can exert its anti-inflammatory properties by inhibiting NETosis and the related molecular pathways. Methods Airway inflammation caused by rhinovirus serotype-1b (RV-1b) was induced in male BALB/c mice. The inflammation was assessed through histological examination and calculation of inflammatory cells present in the bronchoalveolar lavage fluid. Flow cytometry was used to analyze the inflammatory cells and NETotic neutrophils. Western blotting analysis was conducted to detect proteins associated with NETosis, inflammasome activation, and signaling. Furthermore, confocal microscopy was utilized to observe neutrophil extracellular trap (NET) structures in vivo tissues and in vitro neutrophils, neutrophil infiltration, and inflammasome formation. Results The administration of P4 proved to be an effective treatment for reducing airway inflammation and the production of NETs caused by RV-1b infection. The infection triggered the activation of NLRP3 inflammasomes in neutrophils, which led to the maturation of IL-1β and subsequent activation of both the NF-κB and p38 signaling pathways. The activation of NF-κB signaling resulted in the secretion of downstream chemokines CCL3 and IL-6, which led to an increase in neutrophil infiltration into the lung airways. Moreover, the activation of p38 signaling led to the generation of reactive oxygen species, resulting in NETosis. However, the administration of P4 inhibited the activation of the NLRP3 inflammasome, which subsequently led to the deactivation of both the IL-1β-NF-κB and IL-1β-p38 axes. As a result, there was a reduction in neutrophil infiltration and NETosis. Furthermore, TGF-β-activated kinase 1 (TAK1) was identified as an intermediary enzyme. P4 inhibits both the NF-κB and IL-1β-p38 pathways by suppressing the activity of TAK1. Conclusion The capacity of P4 to mitigate rhinovirus-induced airway inflammation is attributed to its ability to impede the infiltration of neutrophils and NETosis. As inflammation mediated by NETosis is widespread in diverse disorders, our findings propose that P4 could potentially function as a universal therapeutic agent in the management of such ailments.
研究领域:
免疫学
·
呼吸病学
·
病毒学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Communication and Signaling
·
2025
·Vol. 23
·期 1
·1-21
·
IF 8.9
Li Lei,Peng Ruilong,Wang Cong,Chen Xin,Gheyret Dilmurat,Guan Siyu,Chen Bo,Liu Yafan,Liu Xilei,Cao Yiyao,Han Cha,Xiong Jianhua,Li Fanjian,Lu Taoyuan,Jia Haoran,Li Kaiji,Wang Jinchao,Zhang Xu,Xu Jianye,Wang Yajuan,Xu Xin,Li Tuo,Zhang Jianning,Zhang Shu
Neutrophils are the first responders among peripheral immune cells to infiltrate the central nervous system following a traumatic brain injury (TBI), triggering neuroinflammation that can exacerbate secondary tissue damage. The precise molecular controls that dictate the inflammatory behavior of neutrophils post-TBI, however, remain largely elusive. Our comprehensive analysis of the molecular landscape surrounding the trauma in TBI mice has revealed a significant alteration in the abundance of β2 integrin (ITGB2), predominantly expressed by neutrophils and closely associated with immune responses. Using the fluid percussion injury (FPI) mouse model, we investigated the therapeutic efficacy of Rovelizumab, an agent that blocks ITGB2. The treatment has demonstrated significant improvements in neurologic function in TBI mice, attenuating blood–brain barrier permeability, mitigating oxidative stress and inflammatory mediator release, and enhancing cerebral perfusion. Moreover, ITGB2 blockade has effectively limited the adherence, migration, and infiltration of neutrophils, and has impeded the formation of neutrophil extracellular traps (NETs) upon their activation. Finally, it was demonstrated that ITGB2 mediates these effects mainly through its interaction with intercellular adhesion molecule-1 (ICAM 1) of endotheliocyte. These findings collectively illuminate ITGB2 as a crucial molecular switch that governs the adverse effects of neutrophils post-TBI and could be targeted to improve clinical outcome in patients.
研究领域:
神经科学
·
免疫学
·
创伤医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）