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neutrophil transcriptional profile changes during transii from bone marrow to sites of inflammation

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Cellular & Molecular Immunology 2015年第1期12卷 53-65页

作者： Flavia S Lakschevitz Michelle B Visser Chunxiang Sun Michael Glogauer Department of Periodontology Faculty of Dentistry University of Toronto Toronto Ont. Canada Matrix Dynamics Group Faculty of Dentistry University of Toronto Toronto Ont. Canada Current address: Department of Oral Biology School of Dental Medicine U niversity at Buffalo The State University of New York Buffalo NY USA

It has recently been established that neutrophils, the most abundant leukocytes, are capable of changes in gene expression during inflammatory responses. However, changes in the transcriptome as the neutrophil leaves the bone marrow have yet to be described. We hypothesized that neutrophils are transcriptionally active cells that alter their gene expression profiles as they migrate into the vasculature and then into inflamed tissues. Our goal was to provide an overview of how the neutrophil＇s transcriptome changes as they migrate through different compartments using microarray and bio-informatic approaches. Our study demonstrates that neutrophils are highly plastic cells where normal environmental cues result in a site-specific neutrophil transcriptome. We demonstrate that neutrophil genes undergo one of four distinct expression change patterns as they move from bone marrow through the circulation to sites of inflammation：（i） continuously increasing; （ii） continuously decreasing; （iii） a down-up-down; and （iv） an up-down-up pattern. Additionally, we demonstrate that the neutrophil migration signaling network and the balance between anti-apoptotic and pro-apoptotic signaling are two of the main regulatory mechanisms that change as the neutrophil transits through compartments.

关键词： fMLP signaling pathway microarray neutrophil transcriptome

neutrophil–macrophage communication via extracellular vesicle transfer promotes itaconate accumulation and ameliorates cytokine storm syndrome

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Cellular & Molecular Immunology 2024年第7期21卷 689-706页

作者： Haixia Kang Ting Liu Yuanyuan Wang Wenjuan Bai Yan Luo Jing Wang Department of Immunology and Microbiology Shanghai Institute of ImmunologyShanghai Jiao Tong University School of MedicineShanghai200025China Department of Anesthesiology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Center for Immune-related Diseases at Shanghai Institute of Immunology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Cytokine storm syndrome(CSS)is a life-threatening systemic inflammatory syndrome involving innate immune hyperactivity triggered by various therapies,infections,and autoimmune ***,the potential interplay between innate immune cells is not fully ***,using poly I:C and lipopolysaccharide(LPS)-induced cytokine storm models,a protective role of neutrophils through the modulation of macrophage activation was identified in a CSS *** imaging revealed neutrophil-derived extracellular vesicles(NDEVs)in the liver and spleen,which were captured by *** suppressed proinflammatory cytokine production by macrophages when cocultured in vitro or infused into CSS *** profiling of macrophages treated with NDEV revealed elevated levels of the anti-inflammatory metabolite,itaconate,which is produced from cis-aconitate in the Krebs cycle by cis-aconitate decarboxylase(Acod1,encoded by Irg1).Irg1 in macrophages,but not in neutrophils,was critical for the NDEV-mediated anti-inflammatory ***,NDEVs delivered miR-27a-3p,which suppressed the expression of Suclg1,the gene encoding the enzyme that metabolizes itaconate,thereby resulting in the accumulation of itaconate in *** findings demonstrated that neutrophil-to-macrophage communication mediated by extracellular vesicles is critical for promoting the anti-inflammatory reprogramming of macrophages in CSS and may have potential implications for the treatment of this fatal condition.

关键词： Cytokine storm syndrome neutrophil Extracellular vesicle Itaconate Macrophage

Association of the neutrophil-to-lymphocyte ratio and prostate cancer detection rates in patients via contemporary multi-core prostate biopsy

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Asian Journal of Andrology 2016年第6期18卷 937-941页

作者： Jong Jin Oh Ohsung Kwon Jung Keun Lee Seok-Soo Byun Sang Eun Lee Sangchul Lee Sung Kyu Hong Department of Urology Seoul National University Bundang Hospital Seongnam Korea.

The aim of this study was to determine whether the neutrophil-to-lymphocyte ratio （NLR）, a measure of the systemic inflammatory response is associated with the overall prostate cancer detection rate in men who underwent contemporary multi （〉12）-core transrectal ultrasound （TRUS） biopsy. We reviewed the records of 3913 patients with initial prostate-specific antigen （PSA） levels ranging from 4 to 10 ng ml^-1 who underwent TRUS-guided prostate biopsy between April 2006 and May 2014. NLR was calculated by prebiopsy neutrophil and lymphocyte counts. We excluded patients who had evidence of acute prostatitis, a history of prostate surgery, and any systemic inflammatory disease. A multivariate logistic regression model was used to analyze prostate cancer detection. After adjusting for confounding factors, predictive values were determined according to the receiver operating characteristic-derived area under the curve, both including and excluding the NLR variable. In univariate analyses, NLR was a significant predictor of prostate cancer detection （P 〈 0.001）. In multivariate analyses, a higher NLR was significantly associated with prostate cancer detection after adjusting for other factors （OR = 1.372, P = 0.038）. The addition of NLR increased the accuracy from 0.712 to 0,725 （P = 0.005） in the multivariate model for prostate cancer detection. NLR may be a potentially useful clinical marker in the detection of prostate cancer among men with a PSA level in the 4-10 ng ml^-1 range. These findings are derived from a retrospective analysis and should be validated in larger populations through prospective studies.

关键词： inflammation lymphocyte neutrophil prostate biopsy prostate cancer

neutrophil-targeted liposomal platform: A shift in novel approach for early detection and treatment of cancer metastasis

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Asian Journal of Pharmaceutical Sciences 2024年第5期19卷 182-201页

作者： Cong Li Kexin Zhang Zehua Cheng Lihong Wang Zehao Li Chao Shen Zhihang Li Zeyu Wang Lianrui Cao Lijiang Chen School of Pharmaceutical Science Liaoning UniversityShenyang 110036China Liaoning Key Laboratory of New Drug Research&Development Shenyang 110036China

Tumormetastasis is responsible for 90%of cancer-associated deaths,and its early detection may decrease the likelihood of *** have demonstrated that metastasis results from the interaction between“seeds”(tumor cells)and“soil”(pre-metastatic niche,PMN).As the first and most abundant immune cells to be recruited to PMN,neutrophils play a key role in the ultimate formation of metastatic foci through mechanisms such as supporting tumor cell growth,promoting angiogenesis,and shaping an immune-suppressive *** this study,two distinct types of sialic acid(SA)-modified liposomes were prepared to target and regulate pro-metastatic neutrophils through the l-selectin *** of these liposomes,named ICG@SAL,was used to encapsulate indocyanine green(ICG)and was specifically designed for the early detection of cancer *** other liposome,referred to as ABE/Cur@SAL,co-loaded abemaciclib(ABE)and curcumin(Cur),with the intention of suppressing the progression of metastatic *** imaging results from the mouse spontaneous metastasis model indicated that ICG@SAL demonstrated faster targeting and stronger accumulation in the metastatic organs than unmodified ICG liposomes(ICG@CL).This suggested that ICG@SAL could detect tumor metastasis at an early *** therapy with co-loaded liposomes in the mouse experimental lung metastasis model indicated that ABE/Cur@SAL could inhibit regulatory T(Treg)cell proliferation,enhance effector T cell activity and reduce tumorigenic factor release,implying that ABE/Cur@SAL could inhibit tumor ***,our work provided a sensitive and convenient approach to early diagnosis and treatment of tumor ***@SAL could be employed for the early detection of tumor metastasis,while ABE/Cur@SAL could be used to inhibit the development of tumor metastasis when early metastasis was identified.

关键词： Lung metastasis Early depletion Liposome neutrophil Sialic acid Pre-metastatic niche

neutrophil gelatinase-associated lipocalin does not predict acute kidney injury in heart failure

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World Journal of Clinical Cases 2020年第9期8卷 1600-1607页

作者： Fiorenza Ferrari Elisa Scalzotto Pasquale Esposito Sara Samoni Flavio Mistrorigo Lilia Maria Rizo Topete Massimo De Cal Grazia Maria Virzì Valentina Corradi Rossella Torregrossa Roberto Valle Stefania Bianzina Nadia Aspromonte Matteo Floris Alessandro Fontanelli Alessandra Brendolan Claudio Ronco Department of Nephrology Dialysis&Transplantation International Renal Research Institute VicenzaSt.Bortolo HospitalVicenza 36100Italy Department of Internal Medicine NephrologyDialysis and Transplantation ClinicsGenoa University and IRCCS Policlinico San MartinoGenova 16132Italy Department of Cardiology Coronary Intensive Care UnitSt.Bortolo HospitalVicenza 36100Italy Department of Cardiology Coronary Intensive Care UnitChioggia HospitalVenezia 36100Italy Neonatal and Pediatric Intensive Care Unit G.Gaslini InstituteGenoa 16147Italy Department of Cardiovascular and Thoracic Sciences Catholic University of the Sacred Heart Agostino Gemelli FoundationRome 00168Italy Division of Nephrology and Dialysis Azienda Ospedaliera G.BrotzuPiazzale Ricchi n°1Cagliari 09134Italy

BACKGROUND Acute cardiorenal syndrome type 1(CRS-1)is defined by a rapid cardiac dysfunction leading to acute kidney injury(AKI).neutrophil gelatinaseassociated lipocalin(NGAL)is expressed on the surface of human neutrophils and epithelial cells,such as renal tubule cells,and its serum(sNGAL)and urinary have been used to predict AKI in different clinical *** To characterize CRS-1 in a cohort of patients with acute heart diseases,evaluating the potentiality of sNGAL as an early marker of *** We performed a retrospective cohort,multi-centre *** January 2010 to December 2011,we recruited 202 adult patients admitted to the coronary intensive care unit(CICU)with a diagnosis of acute heart failure or acute coronary *** monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU *** Overall,enrolled patients were hemodynamically stable with a mean arterial pressure of 92(82-107)mmHg,55/202(27.2%)of the patients developed CRS-1,but none of them required *** the NGAL delta value(AUC 0.40,95%CI:0.25-0.55)nor the NGAL peak(AUC 0.45,95%CI:0.36-0.54)or NGAL cutoff(≥140 ng/mL)values were statistically significant between the two groups(CRS-1 vs no-CRS1 patients).The area under the ROC curve for the prediction of CRS-1 was 0.40(95%CI:0.25-0.55)for the delta NGAL value and 0.45(95%CI:0.36-0.54)for the NGAL peak ***,in multivariate analysis,the risk of developing CRS-1 was correlated with age>60 years,urea nitrogen at admission and 24 h-urine output(AUC 0.83,SE=60.5%SP=93%),while sNGAL was not significantly *** In our population,sNGAL does not predict CRS-1,probably as a consequence of the mild renal injury and the low severity of heart ***,these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.

关键词： Cardiorenal syndrome type 1 Acute kidney injury Biomarker neutrophil gelatinase-associated lipocalin

Synthesis and Expression in Escherichia coli of a Human neutrophil Activating Protein-1/Interleukin-8 Gene

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Science China Chemistry 1993年第10期36卷 1224-1232页

作者：金冬雁徐荣辉周圆王平侯云德 National Laboratory of Molecular Virology & Genetic Engineering Chinese Academy of Preventive Medicine Beijing 100052 PRC

The complete gene coding for human neutrophilactivating protein-1/interleukin-8 was synthesized using a semi-chemical semi-enzymatic method. The synthetic gene was then overexpressed in Escherichia coli under the temperature-regulated control of the P_RP_L tandem promoters. As determined by SDS-PAGE and densitometry, the overexpressed protein comprised up to 18.5% and 10.9% of the total soluble protein in E. coli cells grown in shake flasks and in batch fermentation, respectively. The recombinant NAP-1/IL-8 was then purified to>95% homogeneity by gel filtration and cation exchange chromatography. The purified protein appeared as a single band on the SDS-PAGE gel and possessed potent chemotactic activity in the concentration of <10 ng/ml, as assayed by the agarose plate method. An early skin reactivity was also observed when the pure NAP-1/IL-8 was injected subcutaneously into the rabbits. The N-terminal 36 amino acid sequence of the recombinant NAP1/IL-8 was determined using the Edman method and was shown to be identical to that of the ntive protein.

关键词： neutrophil activating protein-1/interleukin-8 DNA synthesis expression of cloned genes protein sequencing.

An inducible model for specific neutrophil depletion by diphtheria toxin in mice

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Science China(Life Sciences) 2021年第8期64卷 1227-1235页

作者： Tianzhu Chao Liaoxun Lu Lichen Zhang Rong Huang Zhuangzhuang Liu Binhui Zhou Eryan Kong Zhongjian Zhang Toby Lawrence Yinming Liang Institute of Psychiatry and Neuroscience Xinxiang Medical UniversityXinxiang 453003China Henan Key Laboratory of Immunology and Targeted Therapy School of Laboratory MedicineXinxiang Medical UniversityXinxiang 453003China Laboratory of Genetic Regulators in the Immune System Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory MedicineSchool of Laboratory MedicineXinxiang Medical UniversityXinxiang 453003China Centre for Inflammation Biology and Cancer Immunology King s College LondonLondon SE11ULUK

neutrophils are crucial for immunity and play important roles in inflammatory diseases;however,mouse models selectively deficient in neutrophils are limited,and neutrophil-specific diphtheria toxin(DT)-based depletion system has not yet been *** this study,we generated a novel knock-in mouse model expressing diphtheria toxin receptor(DTR)under control of the endogenous Ly6G *** showed that DTR expression was restricted to Ly6G+neutrophils and complete depletion of neutrophils could be achieved by DT treatment at 24-48 h *** characterized the effects of specific neutrophil depletion in mice at steady-state,with acute inflammation and during tumor *** study presents a valuable new tool to study the roles of neutrophils in the immune system and during tumor progression.

关键词： neutrophil immunity depletion

DNA of neutrophil extracellular traps promote NF-κBdependent autoimmunity via cGAS/TLR9 in chronic obstructive pulmonary disease

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3040-3055页

作者： Jun Chen Tao Wang Xiaoou Li Lijuan Gao Ke Wang Mengxin Cheng Zijian Zeng Lei Chen Yongchun Shen Fuqiang Wen Department of Respiratory and Critical Care Medicine West China HospitalWest China School of Medicineand Division of Pulmonary DiseasesState Key Laboratory of BiotherapySichuan UniversityChengduSichuan 610041China

Chronic obstructive pulmonary disease(COPD)is characterised by persistent airway inflammation even after cigarette smoking *** extracellular traps(NETs)have been implicated in COPD severity and acute airway inflammation induced by short-term cigarette smoke(CS).However,whether and how NETs contribute to sustained airway inflammation in COPD remain *** study aimed to elucidate the immunoregulatory mechanism of NETs in COPD,employing human neutrophils,airway epithelial cells(AECs),dendritic cells(DCs),and a long-term CS-induced COPD mouse model,alongside cyclic guanosine monophosphate-adenosine monophosphate synthase and toll-like receptor 9 knockout mice(cGAS-^(−/−)TLR9^(−/−));Additionally,bronchoalveolar lavage fluid(BALF)of COPD patients was *** from COPD patients released greater cigarette smoke extract(CSE)-induced NETs(CSE-NETs)due to mitochondrial respiratory chain *** CSE-NETs,containing oxidatively-damaged DNA(NETs-DNA),promoted AECs proliferation,nuclear factor kappa B(NF-κB)activation,NF-κB-dependent cytokines and type-I interferons production,and DC maturation,which were ameliorated/reversed by silencing/inhibition of cGAS/*** the COPD mouse model,blocking NETs-DNA-sensing via cGAS^(−/−)and TLR9^(−/−)mice,inhibiting NETosis using mitoTEMPO,and degrading NETs-DNA with DNase-I,respectively,reduced NETs infiltrations,airway inflammation,NF-κB activation and NF-κBdependent cytokines,but not type-I interferons due to IFN-α/βreceptor *** NETs components(myeloperoxidase and neutrophil elastase activity)in BALF of COPD smokers correlated with disease severity and NF-κB-dependent cytokine levels,but not type-I interferon *** conclusion,NETs-DNA promotes NF-κB-dependent autoimmunity via cGAS/TLR9 in long-term CS exposure-induced ***,targeting NETs-DNA and cGAS/TLR9 emerges as a potential strategy to alleviate persistent airway inflammation in COPD.

关键词： inflammation TLR9 neutrophil

neutrophil INFILTRATION IS INVOLVED IN 5-FLUOROURACIL INDUCED LIPID PEROXIDATIVE DAMAGE OF THE SMALL INTESTINE

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Chinese Medical Sciences Journal 1997年第3期12卷 181-183页

作者：陈冬利吴国生王为忠王俊义 Department of Gastroenteric Surgery Xijing Hospital Fourth Military Medical University Xi'an 710032.

This study evaluated the mechanisms of 5-fluorouracil (5-FU) induced intestinal damage by investi-gating the lipid peroxide (LPO) level, myeloperoxidase (MPO) activity and disaccharidase activity in *** Ⅰ animals (n=6) were sacrificed and served as a normal control group. Group Ⅱ animaIes (n= 24 )were given a single intraperitoneal injection of 5-FU (150 mg/kg) and every 8 rats were sacrificed on day1,3 and 5 after injection respectively. Results: LPO concentration in blood and intestinal mucosa was sig-nificantly higher in the group Ⅱ than in the group Ⅰ on day 1 and 3 (Pneutrophil infiltration may be involved in 5-FU-induced lipid peroxidative damage of the small intes-tine which was reflected by the decreased disaccharidases activities.

关键词： neutrophil 5-fluorouracil lipid peroxide