Radiation Effects on the Immunological Functions and Membranes of Alveolar Macrophages of Rats

Alveolar macrophages (AM) from BCG activated Wistar rat were irradiated with different doses of Gamma rays in vitro. The effects of radiation on their immunological functions and membrane damage were studied. The non-specific cytotoxicity and specific phagocytosis of AM irradiated with dose of 0, 100, 300 and 500 Gy decreased with the increase in dose. The relative fractions of Lactate Dehydrogenase and Beta-glucuronidase (β-glu) activity in supernatant increased with the increase in dose. There was a correlation between the suppression of immunological functions and the degree of damage of cytoplasmic and lysosomal membranes of AM after irradiation. Na2SeO3, a protective agent of cell membranes, alleviated this effect on the suppressive cytotoxicity indices of irradiated AM.

Voltage-dependent K^+-channel Responses during Activation and Damage in Alveolar Macrophages Induced by Quartz Particles

The roles of voltage-dependent K^＋ channels during activation and damage in alveolar macrophages （AMs） exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage, and were adjusted to 5× 10^5/mL. After AMs were exposed to different concentrations （0, 25, 50, 100, 200 μg/mL） of quartz particles and 100 μg/mL amorphous silica particles for 24 h, the voltage-depended K^＋ current in AMs was measured by using patch clamp technique. Meanwhile the leakage of lactate dehydrogenase （LDH） and the viability of AMs were detected respectively. Patch clamp studies demonstrated that AMs possessed outward delayed and inward rectifying K^＋ current. Exposure to quartz particles increased the outward delayed K^＋ current but it had no effect on inward rectifier K^＋ current in AMs. Neither of the two K^＋ channels in AMs was affected by amorphous silica particles. Cytotoxicity test showed that both silica particles could damage AM membrane and result in significant leakage of LDH （P〈0.05）. MTT studies, however, showed that only quartz particles reduced viability of AMs （P〈0.05）. It is concluded that quartz parti- cles can activate the outward delayed K^＋ channel in AMs, which may act as an activating signal in AMs to initiate an inflammatory response during damage and necrosis in AMs induced by exposure to quartz particle. K^＋ channels do not contribute to the membrane damage of AMs.

Dietary plant extracts modulate gene expression profiles in alveolar macrophages of pigs experimentally infected with porcine reproductive and respiratory syndrome virus

Background: Our previous study showed that 3 plant extracts enhanced the immune responses and growth efficiency of weaned pigs infected with porcine reproductive and respiratory syndrome virus(PRRSV), which is one of the most economically important disease in swine industry. However, each plant extract differently effected on growth efficiency and immune responses. Therefore, the objective of this study was conducted to characterize the effects and investigate the potential underlying mechanisms of 3 plant extracts on gene expression of alveolar macrophages in weaned pigs experimentally infected with PRRSV.Results: PRRSV infection altered(P < 0.05) the expression of 1,352 genes in pigs fed the control(CON;755 up, 597 down). Compared with the infected CON, feeding capsicum(CAP), garlic botanical(GAR), or turmeric oleoresin(TUR) altered the expression of 46 genes(24 up, 22 down), 134 genes(59 up, 75 down), or 98 genes(55 up, 43 down) in alveolar macrophages of PRRSV-infected pigs, respectively. PRRSV infection up-regulated(P < 0.05) the expression of genes related to cell apoptosis, immune system process, and response to stimulus, but downregulated(P < 0.05) the expression of genes involved in signaling transduction and innate immune response.Compared with the infected CON, feeding TUR or GAR reduced(P < 0.05) the expression of genes associated with antigen processing and presentation, feeding CAP up-regulated(P < 0.05) the expression of genes involved in antigen processing and presentation. Supplementation of CAP, GAR, or TUR also enhanced(P < 0.05) the expression of several genes related to amino acid metabolism, steroid hormone synthesis, or RNA degradation, respectively.Conclusions: The results suggest that 3 plant extracts differently regulated the expression of genes in alveolar macrophages of PRRSV-infected pigs, especially altering genes involved in immunity.

Dietary arachidonate in milk replacer triggers dual benefits of PGE2 signaling in LPS-challenged piglet alveolar macrophages

Background: Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE2(supporting both inflammation and resolution) makes it a potent regulator of immune cell function. Therefore, the use of dietary long chain n-6 PUFA to enhance PGE2 effects merits investigation.Methods: Day-old pigs(n = 60) were allotted to one of three dietary groups for 21 d(n = 20/diet), and received either a control diet(CON, arachidonate = 0.5% of total fatty acids), an arachidonate(ARA)-enriched diet(LC n-6,ARA = 2.2%), or an eicosapentaenoic(EPA)-enriched diet(LC n-3, EPA = 3.0%). Alveolar macrophages and lung parenchymal tissue were collected for fatty acid analysis. Isolated alveolar macrophages were stimulated with LPS in situ for 24 h, and m RNA was isolated to assess markers associated with inflammation and eicosanoid production.Culture media were collected to assess PGE2 secretion. Oxidative burst in macrophages was measured by: 1)oxygen consumption and extracellular acidification(via Seahorse), 2) cytoplasmic oxidation and 3) nitric oxide production following 4, 18, and 24 h of LPS stimulation.Results: Concentration of ARA(% of fatty acids, w/w) in macrophages from pigs fed LC n-6 was 86% higher than CON and 18% lower in pigs fed LC n-3(P < 0.01). Following LPS stimulation, abundance of COX-2 and TNF-α mRNA(P < 0.0001), and PGE2 secretion(P < 0. 01) were higher in LC n-6 PAM vs. CON. However, ALOX5 abundance was1.6-fold lower than CON. Macrophages from CON and LC n-6 groups were 4-fold higher in ALOX12/15 abundance(P < 0.0001) compared to LC n-3. Oxygen consumption and extracellular acidification rates increased over 4 h following LPS stimulation(P < 0.05) regardless of treatment. Similarly, increases in cytoplasmic oxidation(P < 0.001)and nitric oxide production(P < 0.002) were observed after 18 h of LPS stimulation but were unaffected by diet.Conclusions: We infer that enriching diets with arachidonic acid may be an effective means to enhance a stronger innate immunologic response to respiratory challenges in neonatal pigs. However, further work is needed to examine long-term safety, clinical efficacy and economic viability.

TNF-α Up-regulates Matrix Metalloproteinase-9 Expression and Activity in Alveolar Macrophages from Patients with Chronic Obstructive Pulmonary Disease

To study the effects of tumor necrosis factor （TNF）-α on matrix metalloproteinase （MMP）-9 expression and activity in alveolar macrophages （AM） and to investigate the role of NF-κB in the induction, AM were collected from bronchoalveolar lavage fluid （BALF） of healthy subjects and patients with chronic obstructive pulmonary disease （COPD）. MMP-9 expression and activity were detected by semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）, Western blotting and zymography. NF-κB activity was detected by electrophoretic mobility shift assay （EMSA）. MMP-9 expression and activity induced by TNF-α in AM from healthy subjects or patients with COPD were significantly increased in a dose-dependent manner （P〈0.05）. NF-κB activity induced by TNF-α was significantly increased in AM from patients with COPD, and pyrrolidine dithiocarbamate （PDTC） and N-acetyl-L-cysteine （NAC） significantly inhibited the activation of NF-κB induced by TNF-α （P〈0.05）. The presents study suggested that the expression and activity of MMP-9 from AM can be induced by TNF-α, and TNF-α/NF-κB signal pathway may play an important role in the induction.

Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3

Objective:To explore the expression of microRNA(miRNA) let-7c and its function in chronic obstructive pulmonary disease(COPD) and alveolar macrophage cells.Methods:Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice.MiRNA let-7c was overexpresscd in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3(STAT3) as well as phosphorylation level of STAT3 after LPS stimulation.Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3.Results:MiRNA let-7c expression was significantly lower in patients with COPD compared with control group,and the similar result was found in COPD mice and LPS stimulated alveolar macrophages.Overexpression of miRNA lct-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha,interleukin-6 and interleukin-1β.Luciferase assay showed STAT3 was a targeting of miRNA lct-7c in alveolar macrophages.Conclusions:MiRNA lct-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage,which may provide a new target for COPD treatment strategies.

Effects of Bilirubin on Alveolar Macrophages in Rats with Emphysema and Expression of iNOS and NO in Them

To explore the effects of bilirubin on alveolar macrophages (AM) and expression of iNOS and NO in them in emphysema model, the rats were pretreated with bilirubin before exposed to smoke. AM were isolated from bronchoalveolar lavage fluid (BALF) and cultured. Pathological microscopic examination of AM and immunohistochemical analysis of iNOS were performed. Nitric oxide (NO) content in the samples was determined by nitrate reductase technique. The results showed both alveoli and alveolar septum appeared normal in size and shape in normal group. AM showed kidney-shaped nucleus and were rich in Golgi complexes and primary lysosomes in the cytoplasm. The inner membrane of mitochondrion was continuous. Most cristae of the mitochondria were intact. In model group, the alveoli were expanded, ruptured and bullaes were formed. Both the population and sizes of AM increased significantly. Secondary lysosomes were rich in the cytoplasm. Deformation and pyknosis of the nucleus, swelling of the mitochondrions and rupture of the inner mitochondrial membrane could also be seen. At high magnification, most of the mitochondrial cristae were broken, or completely lost at certain points. In bilirubin group, alveoli partly expanded and the population of AM also increased, with morphological changes being slighter than that in model group. Both NO contents and expression of iNOS in model group were higher than those in normal group (P<0.05). In bilirubin group the two indice were lower than those in model group (P<0.05). Our findings suggested that high expression of iNOS and high NO content in AM accelerate the development of emphysema associated with smoking in rats. Bilirubin may exert protective effects on AM and retards the development of emphysema in rats.

Induction of matrix metalloproteinase-9 in alveolar macrophages by TNF-α through NF-κB signal pathway

Objective： To explore the effect of tumor necrosis factor （TNF）-α on matrix metalloproteinase-9 （MMP-9） expression and activity in alveolar macrophages （AM） from patients with chronic obstructive pulmonary disease （COPD） and study its associated signal pathway. Methods： AM were collected from bronchoalveolar lavage fluid in patients with COPD. The AM were incubated for 1.5 h with pyrrolidine dithiocarbamate（PDTC） at concentrations from 0 μmol/L to 50μmol/L and then stimulated for 24 h by TNF-α at 10 ng/ml. MMP-9 expression and activity were respectively detected by semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）, Western blotting and Zymography. NF-κB activity was investigated by electrophoretic mobility shift assay （EMSA）. Results： Both the mRNA and protein levels of MMP-9 induced by TNF-α in AM were significantly elevated in a dose dependent manner （ P 〈 0.05）. The level of MMP-9 activity was also correspondingly significantly elevated in the induction （ P 〈 0.05）, which was possibly related with the over-expression of MMP-9. NF-κB activity was significantly increased when AM were stimulated by 10 ng/mL TNF-α （ P 〈 0.05）. The expression of MMP-9 induced by TNF-α could be significantly inhibited by PDTC （P 〈 0.05 ）. Conclusion： The expression and activity of MMP-9 from AM could be induced by TNF-α, and NF-κB signal pathway played an important role in the induction.

Characteristics of alveolar macrophages in bronchioalveolar lavage fluids from active tuberculosis patients identified by single-cell RNA sequencing

Tuberculosis(TB),is an infectious disease caused by Mycobacterium tuberculosis(M.tuberculosis),and presents with high morbidity and mortality.Alveolar macrophages play an important role in TB pathogenesis although there is heterogeneity and functional plasticity.This study aimed to show the characteristics of alveolar macrophages from bronchioalveolar lavage fluid(BALF)in active TB patients.Single-cell RNA sequencing(scRNA-seq)was performed on BALF cells from three patients with active TB and additional scRNA-seq data from three healthy adults were established as controls.Transcriptional profiles were analyzed and compared by differential gene expression and functional enrichment analysis.We applied pseudo-temporal trajectory analysis to investigate correlations and heterogeneity within alveolar macrophage subclusters.Alveolar macrophages from active TB patients at the single-cell resolution are described.We found that TB patients have higher cellular percentages in five macrophage subclusters.Alveolar macrophage subclusters with increased percentages were involved in inflammatory signaling pathways as well as the basic macrophage functions.The TB-increased alveolar macrophage subclusters might be derived from M1-like polarization state,before switching to an M2-like polarization state with the development of M.tuberculosis infection.Cell-cell communications of alveolar macrophages also increased and enhanced in active TB patients.Overall,our study demonstrated the characteristics of alveolar macrophages from BALF in active TB patients by using scRNA-seq.

The heterogeneity of tumor-associated macrophages and strategies to target it

Tumor-associated macrophages(TAMs)are emerging as targets for tumor therapy because of their primary role in promoting tumor progression.Several studies have been conducted to target TAMs by reducing their infiltration,depleting their numbers,and reversing their phenotypes to suppress tumor progression,leading to the development of drugs in preclinical and clinical trials.However,the heterogeneous characteristics of TAMs,including their ontogenetic and functional heterogeneity,limit their targeting.Therefore,in-depth exploration of the heterogeneity of TAMs,combined with immune checkpoint therapy or other therapeutic modalities could improve the efficiency of tumor treatment.This review focuses on the heterogeneous ontogeny and function of TAMs,as well as the current development of tumor therapies targeting TAMs and combination strategies.

Pulmonary alveolar proteinosis induced by X-linked agammaglobulinemia:A case report

BACKGROUND Pulmonary alveolar proteinosis(PAP)and X-linked agammaglobulinemia(XLA)are rare diseases in children.Many theories infer that immunodeficiency can induce PAP,but these reports are almost all review articles,and there is little clinical evidence.We report the case of a child with both PAP and XLA.CASE SUMMARY A 4-month-old boy sought medical treatment due to coughing and difficulty in breathing for>2 wk.He had been hospitalized multiple times due to respiratory infections and diarrhea.Chest computed tomography and alveolar lavage fluid showed typical PAP-related manifestations.Genetic testing confirmed that the boy also had XLA.Following total lung alveolar lavage and intravenous immunoglobulin replacement therapy,the boy recovered and was discharged.During the follow-up period,the number of respiratory infections was significantly reduced,and PAP did not recur.CONCLUSION XLA can induce PAP and improving immune function contributes to the prognosis of children with this type of PAP.

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Clinical approach for pulmonary alveolar proteinosis in children

In this editorial,we discuss the clinical implications of the article by Zhang et al.Pulmonary alveolar proteinosis(PAP)is a rare lung disease characterized by excessive surfactant accumulation in the alveoli.It is classified into four categories:Primary,secondary,congenital,and unclassified forms.Primary PAP is caused by the disruption of granulocyte-macrophage colony-stimulating factor(GM-CSF)receptor signaling,which is necessary for the clearance of surfactant by alveolar macrophages.It is further divided into autoimmune PAP,caused by anti-GM-CSF antibodies blocking alveolar macrophage activation,and hereditary PAP,resulting from mutations in genes encoding GM-CSF receptors.Secondary PAP develops due to conditions affecting the number or function of alveolar macrophages,such as infections,immunodeficiency,hematological disorders,or exposure to inhaled toxins.Congenital PAP is linked to mutations in genes involved in surfactant protein production.Notably,the causes of PAP differ between children and adults.Diagnostic features include a characteristic"crazypaving"pattern on high-resolution computed tomography,accompanied by diffuse ground-glass opacities and interlobular septal thickening.The presence of PAP can be identified by the milky appearance of bronchoalveolar lavage fluid and histological evaluation.However,these methods cannot definitively determine the cause of PAP.Whole lung lavage remains the standard treatment,often combined with specific therapies based on the underlying cause.

Inhibition of M2 tumor-associated macrophages polarization by modulating the Wnt/β-catenin pathway as a possible liver cancer therapy method

The problem of liver cancer is becoming increasingly important due to the epi-demic of metabolic diseases and persistent high alcohol consumption.This deter-mines great attention to the development and improvement of methods for early diagnosis and treatment of liver cancer.Huang et al presented a study in the World Journal of Gastroenterology,in which they showed that the use of the traditional Chinese medicine Calculus bovis(CB)can suppress tumor growth in mice by inhibiting M2 tumor-associated macrophages(TAM)through modulating the activity of the Wnt/β-catenin pathway.The interaction of CB components with the Wnt/β-catenin pathway,M2 TAM polarization,and tumor dynamics were studied using network pharmacology,transcriptomics,and molecular docking.It is now generally accepted that the polarization of TAM and the differentiation of the functions of M1 and M2 phagocytes are of great importance for the progression of neoplasms.It is assumed that M2 TAM promote proliferation and migration of tumor cells.Attempts to medicinally influence the Wnt/β-catenin pathway in order to modulate phagocyte polarization now belong to one of the most promising areas of immunotherapy of oncological diseases.Undoubtedly,the work of the Chinese authors deserves attention and further development.

Sulfated Cyclocarya paliurus polysaccharides exert immunomodulatory potential on macrophages via Toll-like receptor 4 mediated MAPK/NF-κB signaling pathways

The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its potential molecular mechanism were investigated.Results showed that SCP3 at 25-100μg/m L increased viability and improved phagocytosis of RAW264.7 cells.Meanwhile,SCP3 could activate mitogen-activated protein kinase(MAPK)and nuclear factor kappa B(NF-κB)signaling pathways,which increased the phosphorylation of Erk1/2,JNK,p38 and NF-κB p65,promoting secretion of cytokines tumor necrosis factorα(TNF-α),interleukin 6(IL-6)and nitric oxide(NO)as well as the production of reactive oxygen species(ROS).In addition,Toll-like receptor 4(TLR4)receptor inhibitors were able to block the production of NO and TNF-αby SCP3-stimulated macrophages.Based on Western blot analysis and validation using specific inhibitors against MAPK and NF-κB signaling pathways,the results demonstrated that SCP3 induced macrophages activation and enhanced TNF-αand NO production via TLR4-mediated MAPK and NF-κB pathways.In summary,SCP3 has significant immunomodulatory potential.The underlying molecular mechanism was that SCP3 activates macrophages via TLR4 receptors to promote ROS production,which in turn activates the downstream MAPK/NF-κB signaling pathway and then increases the secretion levels of cytokines and NO.

Research Advancements in the Interplay between T3 and Macrophages

3,3′,5-Triiodo-L-thyronine(T3)is a key endocrine hormone in the human body that plays crucial roles in growth,development,metabolism,and immune function.Macrophages,the key regulatory cells within the immune system,exhibit marked“heterogeneity”and“plasticity”,with their phenotype and function subject to modulation by local environmental signals.The interplay between the endocrine and immune systems is well documented.Numerous studies have shown that T3 significantly target macrophages,highlighting them as key cellular components in this interaction.Through the regulation of macrophage function and phenotype,T3 influences immune function and tissue repair in the body.This review comprehensively summarizes the regulatory actions and mechanisms of T3 on macrophages,offering valuable insights into further research of the immunoregulatory effects of T3.

Macrophages:Key players in diabetic wound healing

In this editorial,we discuss the article by Wen et al published.Diabetic foot ulcers are prevalent and serious complications of diabetes,significantly impacting patients’quality of life and often leading to disability or death,thereby placing a heavy burden on society.Effective diabetic wound healing is hindered by an imbalance in macrophage polarization;many macrophages fail to transition from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,which is crucial for tissue remodelling and repair.The wound healing process is both dynamic and complex.Healthy M1 macrophages,which have strong phagocytic abilities,are vital during the inflammatory phase of diabetic wound healing.However,the failure to transition to M2 macrophages during the proliferative phase hinders wound healing.We anticipate the development of new therapies that can repair damaged M1 macrophages during the inflammatory phase and promote M2 macrophage polarization during the proliferative phase,thereby enhancing the overall healing process.

Interactions between myoblasts and macrophages under high glucose milieus result in inflammatory response and impaired insulin sensitivity

BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal muscle.However,despite of the decades of research,whether macrophages infiltration and polarization in skeletal muscle under high glucose(HG)milieus results in the development of IR is yet to be elucidated.C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to stimulation.Further exploration of macrophages'role in myoblasts IR and the dynamics of their infiltration and polarization is warranted.AIM To evaluate interactions between myoblasts and macrophages under HG,and its effects on inflammation and IR in skeletal muscle.METHODS We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical staining.Then,we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG milieus.The effects of myoblasts on macrophages were explored through morphological observation,CCK-8 assay,Flow Cytometry,and enzyme-linked immunosorbent assay.The mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation,CCK-8 assay,Immunofluorescence,and 2-NBDG assay.RESULTS The F4/80 and co-localization of F4/80 and CD86 increased,and the myofiber size decreased in IR group(P<0.01,g=6.26).Compared to Mc group,F4/80+CD86+CD206-cells,tumor necrosis factor-α(TNFα),inerleukin-1β(IL-1β)and IL-6 decreased,and IL-10 increased in McM group(P<0.01,g>0.8).In McM+HG group,F4/80+CD86+CD206-cells,monocyte chemoattractant protein 1,TNFα,IL-1βand IL-6 were increased,and F4/80+CD206+CD86-cells and IL-10 were decreased compared with Mc+HG group and McM group(P<0.01,g>0.8).Compered to M group,myotube area,myotube number and E-MHC were increased in MMc group(P<0.01,g>0.8).In MMc+HG group,myotube area,myotube number,E-MHC,GLUT4 and glucose uptake were decreased compared with M+HG group and MMc group(P<0.01,g>0.8).CONCLUSION Interactions between myoblasts and macrophages under HG milieus results in inflammation and IR,which support that the macrophage may serve as a promising therapeutic target for skeletal muscle atrophy and IR.

Interplay between mesenchymal stem cells and macrophages:Promoting bone tissue repair

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.

Research progress of tumor-associated macrophages in immune checkpoint inhibitor tolerance in colorectal cancer

The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.