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macrophage as cellular vehicles for delivery of nanoparticles

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Journal of Innovative Optical Health Sciences 2014年第3期7卷 91-97页

作者： Song Feng Sisi Cui Jing Jin Yueqing Gu Department of Pharmaceuticai Science School of Pharmacy China Pharmaceutical University24 Tongjia Lane Gulou DistrictNanjing 210009P.R.China

Treatment of malignant brain tumors continues to challenge scientists and clinicians *** of these tumors within the central nervous system(CNS),which is considered a'privileged" organ,can prevent the penetration of chemotherapeutic agents through the blood-brain barrier(BBB).To overcome this limitation,nanoparticles are taken up and transported bymacrophage and then delivered directly into the *** this study,we used macrophage touptake the folate-targeted bifunctional miclles loaded with near-infrared(NIR)dye ICG-Der-01and investigate the dynamic bio-distributions of macrophage after intravenous injection intotumor-bearing *** vitro cellular experiments by confocal microscopy indicated that theuptake of micelles in macrophage was greatly enhanced due to the folate receptor *** bio-distributions of macrophage showed a rapid clearing rate through the liver int estine path *** conclusion,macrophage could potentially be used as nanoparticle drug carriers andrequire further investigation.

关键词： macrophage cllular vehicles nanoparticles micelles.

macrophage LMO7 deficiency facilitates inflammatory injury via metabolic-epigenetic reprogramming

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4785-4800页

作者： Shixin Duan Xinyi Lou Shiyi Chen Hongchao Jiang Dongxin Chen Rui Yin Mengkai Li Yuseng Gou Wenjuan Zhao Lei Sun Feng Qian Shanghai Frontiers Science Center of Drug Target Identification and Delivery National Key Laboratory of Innovative ImmunotherapyEngineering Research Center of Cell&Therapeutic AntibodyMinistry of EducationSchool of PharmacyShanghai Jiao Tong UniversityShanghai 200240China

Inflammatory bowel disease(IBD)is a formidable disease due to its complex ***,as a major immune cell population in IBD,are crucial for gut ***,it is still unveiled how macrophages modulate ***,we found that LIM domain only 7(LMO7)was downregulated in pro-inflammatory macrophages,and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)through K48-mediated ubiquitination in *** an enzyme that regulates glycolysis,PFKFB3 degradation led to the glycolytic process inhibition in macrophages,which in turn inhibited macrophage activation and ultimately attenuated murine ***,we demonstrated that PFKFB3 was required for histone demethylase Jumonji domaincontaining protein 3(JMJD3)expression,thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27(H3K27me3).Overall,our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD *** LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.

关键词： Inflammatory bowel disease macrophage LMO7 Ubiquitination PFKFB3 JMJD3

macrophage-derived exosomes modulate wear particle-induced osteolysis via miR-3470b targeting TAB3/NF-κB signaling

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Bioactive Materials 2023年第8期26卷 181-193页

作者： Baiqi Pan Ziji Zhang Xiaoyu Wu Guoyan Xian Xuantao Hu Minghui Gu Linli Zheng Xiang Li Lingli Long Weishen Chen Puyi Sheng Department of Joint Surgery The First Affiliated Hospital of Sun Yat-sen UniversityChina Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology The First Affiliated Hospital of Sun Yat-Sen UniversityChina Research Center of Translational Medicine The First Affiliated Hospital of Sun Yat-sen UniversityChina Department of Spine Surgery The first affiliated hospital of Sun Yat-sen UniversityChina Universite de Paris CNRSINSERMB3OAParisFrance

Aseptic prosthesis loosening(APL)is one of the most prevalent complications associated with *** main cause is the periprosthetic osteolysis induced by wear ***,the specific mechanisms of crosstalk between immune cells and osteoclasts/osteoblasts during osteolysis are *** this study,we report the role and mechanism of macrophage-derived exosomes in wear particle-induced *** results of exosomes up-taken experiments revealed that osteoblast and mature osteoclasts capture macrophage-derived exosomes(M-Exo).Next-generation sequencing and RT-qPCR on M-Exo revealed that exosomal microRNA miR-3470b was downregulated in wear particle-induced *** results of analysis on Luciferase reporter assays/fluorescence in situ hybridization(FISH)/immunofluorescence(IF)/immunohistochemistry(IHC)and co-culture experiments demonstrated that wear particles induced osteoclast differentiation by increasing the expression of NFatc1 via M-Exo miR-3470b targeting TAB3/NF-κB *** also illustrate that engineered exosomes enriching miR-3470b facilitated to suppressed the osteolysis;the microenvironment enriching with miR-3470b could suppress wear particle-induced osteolysis via inhibition of TAB3/NF-κB in *** summary,our findings indicate that macrophage-derived exosomes transfer to osteoclasts to induce osteolysis in wear particle-induced *** exosomes enriching with miR-3470b might be a novel strategy for the targeting treatment of bone resorption-related diseases.

关键词： Aseptic prothesis loosening Exosome Non-coding RNA macrophage Inflammatory osteolysis

macrophage-mediated tumor-targeted delivery of engineered Salmonella typhimurium VNP20009 in anti-PD1 therapy against melanoma

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3952-3971页

作者： Leyang Wu Lin Li Shufeng Li Lina Liu Wenjie Xin Chenyang Li Xingpeng Yin Xuebo Xu Feifei Bao Zichun Hua The State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing 210023China Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc. Changzhou 213164China School of Biopharmacy China Pharmaceutical UniversityNanjing 210023China Key Laboratory of Developmental Genes and Human Disease in Ministry of Education Department of Biochemistry and Molecular BiologyMedical School of Southeast UniversityNanjing 210009China

Bacterial antitumor therapy has great application potential given its unique characteristics,including genetic manipulation, tumor targeting specificity and immune system modulation. However,the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8+T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8+T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.

关键词： macrophage Salmonella typhimurium VNP20009 Anti-PD1 nanobody Tumor-targeted delivery Immune activation

macrophage-NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes

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Neuroscience Bulletin 2020年第9期36卷 1035-1045页

作者： Hong-Bin Lin Guan-Shan Wei Feng-Xian Li Wen-Jing Guo Pu Hong Ya-Qian Weng Qian-Qian Zhang Shi-Yuan Xu Wen-Bin Liang Zhi-Jian You Hong-Fei Zhang Department of Anesthesiology Zhujiang Hospital of Southern Medical UniversityGuangzhou 510220China Department of Anesthesiology Shenzhen SAMII Medical CenterShenzhen 518118China Department of Anesthesiology The Second Affiliated HospitalShantou University Medical CollegeShantou 515041China University of Ottawa Heart Institute and Department of Cellular and Molecular Medicine University of OttawaOntarioK1NCanada

Ischemic stroke is one of the leading causes of death *** the post-stroke stage,cardiac dysfunction is common and is known as the brain-heart *** mellitus worsens the post-stroke ***-induced systemic inflammation is the major causative factor for the sequential complications,but the mechanism underlying the brain-heart interaction in diabetes has not been *** NLRP3(NLR pyrin domain-containing 3) inflammasome,an important component of the inflammation after stroke,is mainly activated in M1-polarized *** this study,we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 ***,M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic ***,the NLRP3 inflammasome inhibitor CY-09 restored cardiac function,indicating that the Ml-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.

关键词： Ischemic stroke Diabetes mellitus Cardiac dysfunction NLRP3 inflammasome macrophage

macrophage Inflammatory Protein-lalpha mediates Matrix Metalloproteinase-9 enhancement in human adherent monocytes fed with malarial pigment

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Asian Pacific Journal of Tropical Medicine 2011年第12期4卷 925-930页

作者： Giuliana Giribaldi Elena Valente Amina Khadjavi Manuela Polimeni Mauro Prato Dipartimento di Genetica Biologia e BiochimicaFacolta di Medicina e ChirurgiaUniversita degli studi di TorinoTorinoItaly Dipartimento di Genetica Biologia e BiochimicaFacolta di Medicina e ChirurgiaUniversita degli studi di TorinoTurinoItaly Corresponding author:Prof.Mauro Prato PhDDepartment of GeneticsBiology and BiochemistryUniversity of Torino Medical School10126TorinoItaly

Objective:To investigate the role of macrophage inflammatory protein-1alpha(MIP-1 alpha) in the detrimental enhancement of matrix mnetalloproteinase-9(MMP-9) expression,release and activity induced by phagocytosis of malarial pigment(haemozoin,HZ) in human monocytes. Methods:Human adherent monocytes were unfed/fed with native HZ for 2 *** 24 hours. MIP-1 alpha production was evaluated by ELISA in cell *** /fed monocytes were treated in presence/absence of anti-human MIP-1 alpha blocking antibodies or recombinant human MIP-lalpha for 15 h(RNA studies) or 24 h(protein studies): therefore,MMP-9 mRNA expression was evaluated in cell lysatcs by Real Time RT-PCR,whereas proMMP-9 and active MMP-9 protein release were measured in cell supernatants by Western blotting and gelatin ***:Phagocytosis of HZ by human monocytes increased production of MIP-1 *** expression of MMP-9 and protein release of proMMP-9 and active *** the HZ-enbancing effects on MMP-9 were abrogated by anti-human MIP- 1 alpha blocking antibodies and mimicked by recombinant human MIP-l ***: The present work suggests a role for MIP-lalpha in the HZ-dependent enhancement of MMP-9 expression,release and activity observed in human *** new detrimental effects of HZ-triggered proinflammatory response by phagocytic cells in falciparum malaria.

关键词： Plasmodium falciparum Malaria Monocyte Phagocytosis Haemozoin Matrix metalloproteinase-9 macrophage inflammatory proteinlalpha

macrophage Phenotypes and Hepatitis B Virus Infection

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Journal of Clinical and Translational Hepatology 2020年第4期8卷 424-431页

作者： Yujia Li Shilin Li Xiaoqiong Duan Chunhui Yang Min Xu Limin Chen Institute of Blood Transfusion Chinese Academy of Medical Sciences and Peking Union Medical CollegeChengduSichuanChina Toronto General Research Institute University of TorontoTorontoON M5G 1L6Canada

Globally, hepatitis B virus (HBV) infection and its related liver diseases account for 780,000 deaths every year. Outcomes of HBV infection depend on the interaction between the virus and host immune system. It is becoming increasingly apparent that Kupffer cells (KCs), the largest population of resident and monocyte-derived macrophages in the liver, contribute to HBV infection in various aspects. These cells play an important role not only in the anti-HBV immunity including virus recognition, cytokine production to directly inhibit viral replication and recruitment and activation of other immune cells involved in virus clearance but also in HBV outcome and progression, such as persistent infection and development of end-stage liver diseases. Since liver macrophages play multiple roles in HBV infection, they are directly targeted by HBV to benefit its life cycle. In the present review, we briefly outline the current advances of research of macrophages, especially the studies of their phenotypes, in chronic HBV infection.

关键词： Hepatitis B virus Chronic HBV infection macrophage Phenotype

macrophage regulation of graft-vs-host disease

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World Journal of Clinical Cases 2020年第10期8卷 1793-1805页

作者： Ya-Qun Hong Bo Wan Xiao-Fan Li Fujian Institute of Hematology Fujian Provincial Key Laboratory on HematologyDepartment of HematologyFujian Medical University Union HospitalFuzhou 350000Fujian ProvinceChina Faculty of Life Sciences and Medicine King’s College LondonLondon WC1N 3BGUnited Kingdom INSERM U1160 Hospital Saint LouisUniversitéParis DiderotParis 94430France

Hematopoietic stem cell transplantation has become a curative choice of many hematopoietic malignancy,but graft-vs-host disease(GVHD)has limited the survival quality and overall survival of hematopoietic stem cell *** of the immune cells’reaction in pathophysiology of GVHD has improved,but a review on the role of macrophages in GVHD is still *** have observed that macrophage infiltration is associated with GVHD occurrence and *** this review,we summarize and analyze the role of macrophages in GVHD based on pathophysiology of acute and chronic GVHD,focusing on the macrophage recruitment and infiltration,macrophage polarization,macrophage secretion,and especially interaction of macrophages with other immune *** could conclude that macrophage recruitment and infiltration contribute to both acute and chronic *** on distinguishing pathology of acute and chronic GVHD,macrophages tend to show a higher M1/M2 ratio in acute GVHD and a lower M1/M2 ratio in chronic ***,the influence of dominant cytokines in GVHD is controversial and inconsistent with macrophage *** addition,interaction of macrophages with alloreactive T cells plays an important role in acute ***,the interaction among macrophages,B cells,fibroblasts,and CD4+T cells participates in chronic GVHD development.

关键词： macrophage Graft-vs-host disease Hematopoietic stem cell transplantation Polarization Cytokine Regulation

macrophage migration inhibitory factor as a potential prognostic factor in gastric cancer

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World Journal of Gastroenterology 2015年第34期21卷 9916-9926页

作者： Long-Jun He Dan Xie Pin-Jin Hu Yi-Ji Liao Hai-Xia Deng Hsiang-Fu Kung Sen-Lin Zhu Department of Gastroenterology the First Affiliated HospitalSun Yat-sen University Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Stanley Ho Center for Emerging Infectious Diseases and Li Ka Shing Institute of Health Sciences State Key Laboratory of Oncology in South China The Chinese university of Hong Kong

AIM:To investigate macrophage migration inhibitory factor(MIF) expression and its clinical relevance in gastric cancer,and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS:Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry(IHC) semiquantitatively,and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcriptionpolymerase chain reaction(RT-PCR) and Western blot. Two pairs of si RNA targeting the MIF gene(MIF si-1 and MIF si-2) and one pair of scrambled si RNA as a negative control(NC) were designed and chemically synthesized. All si RNAs were transiently transfected in AGS cells with OligofectamineTM to knock down the MIF expression,with the NC group and mock group(OligofectamineTM alone) as controls. At 24,48,and 72 h after transfection,MIF m RNA was analyzed by RTPCR,and MIF and proliferating cell nuclear antigen(PCNA) proteins were detected by Western *** proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium(MTT) assay and colony forming ***:The tissue microarray was informative for IHC staining,in which the MIF expression in gastric cancer tissues was higher than that in adjacent noncancer normal tissues(P < 0.001),and high level of MIF was related to poor tumor differentiation,advanced T stage,advanced tumor stage,lymph node metastasis,and poor patient survival(P < 0.05 for all). After si RNA transfection,MIF m RNA was measured by real-time PCR,and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group,MIF expression was knocked down successfully in gastric cancer cells,and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection,and colonies formed were assayed by

关键词： macrophage migration inhibitory factor Proliferati