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Biomedicines
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30 Years of Alternative Macrophage Activation—a Simple Complexity
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30 Years of Alternative Macrophage Activation—a Simple Complexity

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 9769

Special Issue Editor

Dr. Alexei Gratchev

E-Mail Website
Guest Editor
N.N. Blokhin Cancer Research Center, Institute of Carcinogenesis, 115478 Moscow, Russia
Interests: macrophages; regulation of homeostasis; tumor associated macrophages; chronic inflammation; macrophage plasticity; macrophage molecular markers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Three decades ago, a highly important paper from the lab of Prof. Siamon Gordon appeared in the Journal of Experimental Medicine, describing the effects of IL-4 on the expression of the macrophage mannose receptor (J Exp Med. 1992 Jul 1;176(1):287-92.  doi: 10.1084/jem.176.1.287). This study, which introduced the term “alternative macrophage activation”, became a milestone in immunity research and a foundation for a new concept of macrophage activation. Several years later, alternatively activated macrophages were re-named as type 2 macrophages, and the concept of macrophage activation dichotomy was extended significantly, leading to an explosive growth of studies dedicated to macrophage activation and polarization. Many additional macrophage phenotypes, sub-phenotypes, and activation states were described. Various experimental systems were used to characterize peculiarities of macrophage biology, including macrophage tolerance and macrophage training.

In this issue, we plan to collect the latest advances in macrophage biology research, and to open new horizons by defining new markers as well as diagnostic and therapeutic approaches.

Dr. Alexei Gratchev
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • macrophage
  • monocyte
  • inflammation
  • cancer
  • cytokine
  • atherosclerosis
  • infection
  • healing
  • tolerance

Published Papers (3 papers)

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Research

24 pages, 8601 KiB  
Article
Transcriptomic Analysis of Macrophage Polarization Protocols: Vitamin D3 or IL-4 and IL-13 Do Not Polarize THP-1 Monocytes into Reliable M2 Macrophages
by Maria Rynikova, Petra Adamkova, Petra Hradicka, Jana Stofilova, Denisa Harvanova, Jana Matejova and Vlasta Demeckova
Biomedicines 2023, 11(2), 608; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11020608 - 17 Feb 2023
Viewed by 4414
Abstract
Two main types of macrophages (Mφ) include inflammatory (M1) and anti-inflammatory (M2) macrophages. These cells can be obtained in vitro by polarization of monocytic cell lines using various stimuli. Since there is currently no consensus on the best method for the acquisition of [...] Read more.
Two main types of macrophages (Mφ) include inflammatory (M1) and anti-inflammatory (M2) macrophages. These cells can be obtained in vitro by polarization of monocytic cell lines using various stimuli. Since there is currently no consensus on the best method for the acquisition of reliable M1 and M2 macrophages from the THP-1 cell line, we decided to compare three different polarization protocols at the transcriptomic level. Whole transcriptomes of Mφ polarized according to the chosen protocols were analyzed using RNA-seq. Differential expression of genes and functional enrichment for gene ontology terms were assessed. Compared with other protocols, M1 macrophages polarized using PMA (61.3 ng/mL) and IFN-γ along with LPS had the highest expression of M1-associated regulatory genes and genes for M1 cytokines and chemokines. According to the GO enrichment analysis, genes involved in defensive and inflammatory processes were differentially expressed in these Mφ. However, all three chosen protocols which use Vit D3, IL-13/IL-4, and IL-4, respectively, failed to promote the polarization of macrophages with a reliable M2 phenotype. Therefore, optimization or development of a new M2 polarization protocol is needed to achieve macrophages with a reliable anti-inflammatory phenotype. Full article
(This article belongs to the Special Issue 30 Years of Alternative Macrophage Activation—a Simple Complexity)
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17 pages, 4941 KiB  
Article
EMR1/ADGRE1 Expression in Cancer Cells Upregulated by Tumor-Associated Macrophages Is Related to Poor Prognosis in Colorectal Cancer
by Rokeya Akter, Kwangmin Kim, Hye Youn Kwon, Youngwan Kim, Young Woo Eom, Hye-mi Cho and Mee-Yon Cho
Biomedicines 2022, 10(12), 3121; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123121 - 02 Dec 2022
Cited by 3 | Viewed by 2164
Abstract
EMR1, a member of the adhesion G protein-coupled receptor family (ADGRE1), is a macrophage marker that is abnormally expressed in cancer cells. However, its clinical significance in colorectal cancer (CRC) is not well-known. In this investigation, EMR1 expression in tumor cells (EMR1-TC) was [...] Read more.
EMR1, a member of the adhesion G protein-coupled receptor family (ADGRE1), is a macrophage marker that is abnormally expressed in cancer cells. However, its clinical significance in colorectal cancer (CRC) is not well-known. In this investigation, EMR1 expression in tumor cells (EMR1-TC) was found in 91 (22.8%) of the 399 CRC samples tested by immunohistochemical staining and showed a significant relationship with lymph node metastasis. Furthermore, EMR1-TC was significantly associated with CD68+ CD163+ tumor-associated macrophages (TAMs), and CRC with a high combined EMR1-TC+CD68+CD163+ score showed worse recurrence-free survival prognosis. In an in vitro co-culture assay of colon cancer cells with myeloid cells, we found that EMR1 expression significantly upregulated in cancer cells was induced by macrophages. In addition, there was increased expression of M2 markers (CD163 and interleukin-6 & 10) in myeloid portion, while that of M1 markers (CD86 and iNOS) remained unchanged. Accordingly, upon treatment with M2 macrophage polarization inhibitors (O-ATP, trametinib, bardoxolone methyl), EMR1 expression reduced significantly, along with M2 markers (CD163 and interleukin-6 & 10). In conclusion, EMR1-TC was a high-risk factor for lymph node metastasis and correlated with poor recurrence free survival, particularly in patients with TAM-rich CRC. Furthermore, EMR1 expression in colon cancer cells may be related to M2 macrophage polarization and vice versa. Full article
(This article belongs to the Special Issue 30 Years of Alternative Macrophage Activation—a Simple Complexity)
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15 pages, 2124 KiB  
Article
Prognostic Significance of the Microbiome and Stromal Cells Phenotype in Esophagus Squamous Cell Carcinoma
by Olga Kovaleva, Polina Podlesnaya, Madina Rashidova, Daria Samoilova, Anatoly Petrenko, Valeria Mochalnikova, Vladimir Kataev, Yuri Khlopko, Andrey Plotnikov and Alexei Gratchev
Biomedicines 2021, 9(7), 743; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9070743 - 28 Jun 2021
Cited by 8 | Viewed by 2312
Abstract
Esophageal cancer is one of the most aggressive malignant neoplasms, with low survival rates and limited treatment options. In this study we analyzed the microbiome composition and the phenotype of inflammatory tumor infiltrate in squamous cell carcinoma of esophagus (ESCC) and examined possible [...] Read more.
Esophageal cancer is one of the most aggressive malignant neoplasms, with low survival rates and limited treatment options. In this study we analyzed the microbiome composition and the phenotype of inflammatory tumor infiltrate in squamous cell carcinoma of esophagus (ESCC) and examined possible relationships between them and their prognostic significance. We found that the predominant phyla of microorganisms found in both tumors and adjacent normal tissues were Firmicutes, Proteobacteria, Actinobacteria, Gemmatimonadetes and Bacteroidetes. We established that only bacteria of the genus Staphylococcus differ between tumors and normal tissues. We found a significant correlation between bacterial burden and the phenotype of the tumor stroma. Namely, a group of tumors characterized by a high expression of CD206 (r = −0.3976, p = 0.0056) in the stroma and iNOS (r = −0.2953, p = 0.0439) in tumor cells is characterized by a higher bacterial burden. Further, we established that in the group with a high content of CD206+ macrophages, there is also a predominance of gram-positive bacteria over gram-negative ones. We found that gram-positive bacterial burden is associated with disease prognosis in ESCC showing high content of CD206+ macrophages. In conclusion we established that the tumor microbiome, can be prognostically significant for ESCC when combined with other stromal markers. Full article
(This article belongs to the Special Issue 30 Years of Alternative Macrophage Activation—a Simple Complexity)
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