Dataset Information

Distinct Migratory Properties of M1, M2, and Resident Macrophages Are Regulated by ?_D?₂ and ?_M?₂ Integrin-Mediated Adhesion.

ABSTRACT: Chronic inflammation is essential mechanism during the development of cardiovascular and metabolic diseases. The outcome of diseases depends on the balance between the migration/accumulation of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in damaged tissue. The mechanism of macrophage migration and subsequent accumulation is still not fully understood. Currently, the amoeboid adhesion-independent motility is considered essential for leukocyte migration in the three-dimensional environment. We challenge this hypothesis by studying the contribution of leukocyte adhesive receptors, integrins ?_M?₂, and ?_D?₂, to three-dimensional migration of M1-polarized, M2-polarized, and resident macrophages. Both integrins have a moderate expression on M2 macrophages, while ?_D?₂ is upregulated on M1 and ?_M?₂ demonstrates high expression on resident macrophages. The level of integrin expression determines its contribution to macrophage migration. Namely, intermediate expression supports macrophage migration, while a high integrin density inhibits it. Using in vitro three-dimensional migration and in vivo tracking of adoptively-transferred fluorescently-labeled macrophages during the resolution of inflammation, we found that strong adhesion of M1-activated macrophages translates to weak 3D migration, while moderate adhesion of M2-activated macrophages generates dynamic motility. Reduced migration of M1 macrophages depends on the high expression of ?_D?₂, since ?_D-deficiency decreased M1 macrophage adhesion and improved migration in fibrin matrix and peritoneal tissue. Similarly, the high expression of ?_M?₂ on resident macrophages prevents their amoeboid migration, which is markedly increased in ?_M-deficient macrophages. In contrast, ?_D- and ?_M-knockouts decrease the migration of M2 macrophages, demonstrating that moderate integrin expression supports cell motility. The results were confirmed in a diet-induced diabetes model. ?_D deficiency prevents the retention of inflammatory macrophages in adipose tissue and improves metabolic parameters, while ?_M deficiency does not affect macrophage accumulation. Summarizing, ?₂ integrin-mediated adhesion may inhibit amoeboid and mesenchymal macrophage migration or support mesenchymal migration in tissue, and, therefore, represents an important target to control inflammation.

SUBMITTER: Cui K

PROVIDER: S-EPMC6262406 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Distinct Migratory Properties of M1, M2, and Resident Macrophages Are Regulated by αDβ2 and αMβ2 Integrin-Mediated Adhesion.

Cui Kui K Ardell Christopher L CL Podolnikova Nataly P NP Yakubenko Valentin P VP

Frontiers in immunology 20181115

Chronic inflammation is essential mechanism during the development of cardiovascular and metabolic diseases. The outcome of diseases depends on the balance between the migration/accumulation of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in damaged tissue. The mechanism of macrophage migration and subsequent accumulation is still not fully understood. Currently, the amoeboid adhesion-independent motility is considered essential for leukocyte migration in the three-dimensional en ...[more]

PMID: 30524429

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Project description:Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for the characterisation of macrophage polarisation in situ. Furthermore, CD163 cannot be considered a reliable M2 marker when used on its own.

Dataset Information

Distinct Migratory Properties of M1, M2, and Resident Macrophages Are Regulated by ?_D?₂ and ?_M?₂ Integrin-Mediated Adhesion.

Publications

Distinct Migratory Properties of M1, M2, and Resident Macrophages Are Regulated by α<sub>D</sub>β<sub>2</sub> and α<sub>M</sub>β<sub>2</sub> Integrin-Mediated Adhesion.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Distinct Migratory Properties of M1, M2, and Resident Macrophages Are Regulated by ?D?2 and ?M?2 Integrin-Mediated Adhesion.

Publications

Distinct Migratory Properties of M1, M2, and Resident Macrophages Are Regulated by α<sub>D</sub>β<sub>2</sub> and α<sub>M</sub>β<sub>2</sub> Integrin-Mediated Adhesion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Distinct Migratory Properties of M1, M2, and Resident Macrophages Are Regulated by ?_D?₂ and ?_M?₂ Integrin-Mediated Adhesion.