Background: Macrophage polarization is involved in the development of many diseases such as obesity, diabetes, and cancer. This study aimed to understand the trends and hotspots of macrophage polarization research. Methods: We searched through the Web of Science Core Collection database to obtain original articles in this research domain. CiteSpace, HistCite, and VOSviewer software were used to facilitate the analysis and visualization of scientific productivity and emerging trends. Results: The survey included 3064 articles, and the annual number of publications exhibited an exponential increase. These articles have received a total of 74,801 citations, and the number of annual citations grew from 68 to 18,074 in a decade. Research on macrophage polarization was performed in 76 countries, and the USA ranked first in terms of research output by contributing 1129 (36.8%) articles. The USA also had the highest H-index, total citations, and highly cited article number. PLOS One, Journal of Immunology, and Scientific Reports were the three journals that published the most articles. Interdisciplinary research areas involving macrophage polarization, such as biomaterials, cancer, and diabetes, were identified by journal citation analysis. The top 20 most productive institutions were located mainly in the USA, France, and China, and top authors originated mainly from the USA and Italy. Tumor biology, obesity, and infection were research hotspots and may be promising in the next few years. Conclusions This study provides a comprehensive analysis that delineates the scientific productivity, collaboration, and research hotspots of macrophage polarization research.
Bibliometrics ; Biomedical Research ; Cell Polarity ; physiology ; Efficiency ; Humans ; Macrophages ; physiology

No abstract available.
Calcium Signaling/physiology* ; Cell Polarity/physiology* ; Epithelial Cells/physiology* ; Epithelial Cells/cytology*

In order to carry out their physiological functions, the cells of transporting epithelial tissues must be able to polarize their cell surface domains. Different collections of membrane transport proteins must be distributed to distinct domains of the plasma membrane, and cells must be coupled to one-another through junctional complexes that help organize polarized domains and regulate the permeability of the paracellular pathway. This exquisite organization requires that epithelial cells possess a sorting apparatus that can target newly synthesized transport proteins to the appropriate surface domains. Furthermore, the transport proteins themselves must possess information embedded within their structures that specifies their sites of ultimate functional residence. The nature of this information, and of the protein-protein interactions involved in its interpretation, is beginning to be elucidated. The initial formation of the polarized state involves signaling cascades that epithelial cells use to orient themselves to sites of cell-cell and cell-matrix contact. Recent evidence suggests that one component of these cascades is a kinase that also serves as a cellular energy sensor.
Animals ; Cell Polarity ; Epithelial Cells ; physiology ; Humans ; Membrane Transport Proteins ; physiology ; Protein Transport ; Signal Transduction

Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and are critical for cancer initiation and progression. MicroRNAs (miRNAs) could notably influence the phenotype of TAMs through various targets and signal pathways during cancer progression due to their post-transcriptional regulation. In this review, we discuss mainly the regulatory function of miRNAs on macrophage differentiation, functional polarization, and cellular crosstalk. Firstly, during the generation process, miRNAs take part in the differentiation from myeloid cells to mature macrophages, and this maturation process directly influences their recruitment into the TME, attracted by tumor cells. Secondly, macrophages in the TME can be either tumor-promoting or tumor-suppressing, depending on their functional polarization. Large numbers of miRNAs can influence the polarization of macrophages, which is crucial for tumor progression, including tumor cell invasion, intravasation, extravasation, and premetastatic site formation. Thirdly, crosstalk between tumor cells and macrophages is essential for TME formation and tumor progression, and miRNAs can be the mediator of communication in different forms, especially when encapsulated in microvesicles or exosomes. We also assess the potential value of certain macrophage-related miRNAs (MRMs) as diagnostic and prognostic markers, and discuss the possible development of MRM-based therapies.
Cell Communication ; Cell Differentiation ; Cell Polarity ; Humans ; Macrophages/physiology* ; MicroRNAs/physiology* ; Myeloid Cells/cytology* ; Neoplasms/therapy* ; Tumor Microenvironment

Macrophages are heterogeneous and diversified, and can be polarized into different phenotypes in various microenvironments and physiological or pathological conditions. Major macrophage subpopulations including classically activated(M1) and alternatively activated(M2) macrophages, which represent different surface receptors, secret different cytokines and chemokines, are regulated by different signal paths of transcriptions and epigenetic levels, and play distinctive roles in tumor progress. TCMs may improve the microenvironment by regulating phenotype polarization of macrophages. So far, specific biomarkers and polarized molecules mechanisms generated through the macrophage polarization approach are still unclear. In this article, we merely summarize the advance in domestic and foreign studies on phenotype polarization of macrophages and regulatory mechanisms and look into the future of intervention with TCMs.
Animals ; Cell Polarity ; Humans ; Macrophages ; physiology ; Medicine, Chinese Traditional ; Neoplasms ; drug therapy ; immunology ; Phenotype

To investigate the role of ion channels in the coupling responses of neutrophils to extracellular stimulus, it is necessary to study the membrane ion channel activities using patch-clamp technique. However, little has been known about the ion channel activities in neutrophils due to the difficulties in forming giga-seal with pipettes because of small diameter of neutrophils and the easily developed polarization. Some studies indicated that favorable results could be achieved through pretreatment at low temperature before electrophysiological recordings. But it remains unclear whether the pretreatment affects the membrane current and why the seal rate increases after low temperature pretreatment. The purpose of this study was to investigate the effects of 4 degrees C pretreatment on the membrane current and cell polarity in human neutrophils. In the experiments, human neutrophils were isolated from fresh peripheral blood of healthy volunteers and divided into two groups (room temperature group and 4 degrees C pretreatment group). Voltage-dependent K(+) (Kv) currents were recorded in whole-cell voltage-clamp mode and large-conductance Ca(2+)-activated K(+) (BK(Ca)) currents were recorded using inside-out patches. The results showed that 4 degrees C pretreatment significantly inhibited cell polarity (P<0.05), and it took more time for neutrophils to form a polarity-cycle [(534+/-32) s, n=20] compared with those at room temperature [(257+/-24) s, n=20]. Meanwhile, seal rate significantly increased in 4 degrees C pretreatment group (64%) compared with that in the room temperature group (27.5%). The seal rate and cell polarity rate during 0 approximately 1 min after 4 degrees C pretreatment were significantly different from those at room temperature, while no significant difference was found during 9 approximately 10 min between the two groups. Our results suggest that 4 degrees C pretreatment can inhibit cell polarity and increase seal rate, but has no effects on membrane currents. It is also suggested that 0 approximately 1 min after 4 degrees C pretreatment is a more suitable time for electrophysiological recording in neutrophils.
Cell Polarity ; Cold Temperature ; Humans ; Large-Conductance Calcium-Activated Potassium Channels ; physiology ; Membrane Potentials ; Neutrophils ; physiology ; Potassium Channels, Voltage-Gated ; physiology

Stem cells use asymmetric and symmetric cell division to generate progeny. Symmetric cell division is defined as the generation of daughter cells that are destined to acquire the same fate. Stem cells divide asymmetrically to generate one daughter with a stem-cell fate and one daughter with different fate. Disruption of the machinery that regulates asymmetric division may be a reason for the generation of cancer. The asymmetric mechanism is maintained by cell polarity factors, cell fate determinants, and the spindle apparatus. The mutation or dysregulation of these factors may change stem cells from asymmetric to symmetric cell division, then leading to tumorigenesis. Therefore, further study is needed on the mechanisms of stem cell control between asymmetric and symmetric cell division, as well as the relationships among stem cells, cancer stem cells, and tumor cells. It may bring us a new approach for the resistance, recurrence, and metastasis of tumors.
Animals ; Cell Division ; physiology ; Cell Polarity ; Cell Transformation, Neoplastic ; Drosophila ; cytology ; Humans ; Neoplasms ; pathology ; Neoplastic Stem Cells ; pathology ; Neurons ; cytology ; Spindle Apparatus ; metabolism ; Tumor Suppressor Proteins ; metabolism

This study aimed to establish an animal model of decompression-induced lung injury (DILI) secondary to repetitive diving in mice and explore the role of macrophages in DILI and the protective effects of high-concentration hydrogen (HCH) on DILI. Mice were divided into three groups: control group, DILI group, and HCH group. Mice were exposed to hyperbaric air at 600 kPa for 60 min once daily for consecutive 3 d and then experienced decompression. In HCH group, mice were administered with HCH (66.7% hydrogen and 33.3% oxygen) for 60 min after each hyperbaric exposure. Pulmonary function tests were done 6 h after decompression; the blood was harvested for cell counting; the lung tissues were harvested for the detection of inflammatory cytokines, hematoxylin and eosin (HE) staining, and immunohistochemistry; western blotting and polymerase chain reaction (PCR) were done for the detection of markers for M1 and M2 macrophages. Our results showed that bubbles formed after decompression and repeated hyperbaric exposures significantly reduced the total lung volume and functional residual volume. Moreover, repetitive diving dramatically increased proinflammatory factors and increased the markers of both M1 and M2 macrophages. HCH inhalation improved lung function to a certain extent, and significantly reduced the pro-inflammatory factors. These effects were related to the reduction of M1 macrophages as well as the increase in M2 macrophages. This study indicates that repetitive diving damages lung function and activates lung macrophages, resulting in lung inflammation. HCH inhalation after each diving may be a promising strategy for the prevention of DILI.
Animals ; Cell Polarity ; Diving/adverse effects* ; Lung/physiology* ; Lung Injury/etiology* ; Macrophages/physiology* ; Male ; Mice ; Mice, Inbred BALB C ; Pulmonary Edema/etiology*

AIMAcetylcholine(ACh) is a neurotransmitter and a potent vasodilator in many vascular beds. ACh hyperpolarizes the smooth muscle cells(SMCs) of arteries including the cochlear spiral modiolar artery(SMA) via an endothelium-dependent mechanism, but the biochemical and biophysical basis of the hyperpolarization and vasodilation remain unclear and controversial.

METHODSUsing intracellular recording techniques and an in vitro preparation of the SMA, the ionic mechanism of the hyperpolarization and a possible role of nitric oxide(NO) were investigated.

RESULTSWith 5 mmol/L K(+) in the bathing solution and a minimum longitudinal tension, ACh (0.1-10 micromol/L) induced a robust hyperpolarization in low RP cells but caused a depolarization in the high RP cells. The ACh hyperpolarization was fast in onset and offset and the amplitude was concentration-dependent(22 and 30 mV by 1 micromol/L and 10 micromol/L ACh, respectively, n = 7 ). ACh also hyperpolarized the cells that initially had a high resting potential (RP) but were pre-depolarized by Ba(2+) (50-100 micromol/L). The onset time courses of the hyperpolarization were often slower in these cases than those without the presence of Ba(2+) . The ACh-induced hyperpolarization was blocked by atropine (0.1- 1 micromol/L, n = 6) or DAMP (50 -100 nmol/L, n = 6, a selective M3 antagonist) and also by BAPTA-AM (10 micromol/L, n = 7, a membrane-permeable Ca(2+)-chelator), or charybdotoxin plus apamin (50-100 nmol/L, n= 4, Ca(2+) -activated K(+) -channel blockers), but not by Nomega-nitro-L-arginine methyl ester (L-NAME, 300 micromol/L, n = 8, an inhibitor of NO-synthase), glipizide (10 micromol/L, n = 4, ATP-sensitive K(+) -channel blocker) and indomethacin (10 micromol/L, n = 4, cyclo-oxygenase inhibitor).

CONCLUSIONIt is concluded that ACh-induced hyperpolarization in the arterial SMCs is primarily due to an activation of calcium-activated potassium channels via M3 receptors of endothelial cell and is independent of NO-release in the spiral modiolar artery.

Acetylcholine ; physiology ; Animals ; Arteries ; Cell Polarity ; physiology ; Cochlea ; blood supply ; physiology ; Guinea Pigs ; Membrane Potentials ; physiology ; Muscle, Smooth, Vascular ; metabolism ; physiology ; Nitric Oxide ; metabolism ; Potassium Channels, Calcium-Activated ; metabolism ; Receptor, Muscarinic M3 ; metabolism

OBJECTIVE: This study aims to investigate whether dexamethasone (DEX) can down-regulate the PAR complex and disrupt the cell polarity in the palatal epithelium during palatal fusion. METHODS: Pregnant rats were randomly divided into control and DEX groups, which were injected intraperitoneally with 0.9% sodium chloride (0.1 mL) and DEX (6 mg·kg ⁻¹), respectively, every day from E10 to E12. The palatal epithelial morphology was observed using hematoxylin and eosin staining and scanning electron microscopy. Immunofluorescence staining, Western Blot analysis, and real-time polymerase chain reaction were performed to detect the expression of PAR3, PAR6, and aPKC. RESULTS: The incidence of cleft palate in DEX group (46.15%) was significantly higher than that in control group (3.92%), and the difference was statistically significant (χ2=24.335, P=0.00). DEX can also retard the growth of the palatal shelves and the short palatal shelves. The morphology and arrangement of MEE cells changed from polarized bilayer cells to nonpolarized monolayer ones. Additionally, the spherical structure decreased, which caused the cleft palate. PAR3 and PAR6 were only detected in the palatal epithelium, and aPKC was expressed in the palatal epithelium and mesenchyme. DEX can reduce the expression levels of PAR3, PAR6, and aPKC in the protein and gene levels. CONCLUSIONS DEX can down-regulate the complex gene expression in the MEE cells, thereby destroying the cell polarity and causing cleft palate.
Animals ; Carrier Proteins ; physiology ; Cell Polarity ; drug effects ; Cleft Palate ; etiology ; Dexamethasone ; pharmacology ; Epithelial Cells ; drug effects ; Female ; Glucocorticoids ; pharmacology ; Palate ; Pregnancy ; Rats