M1-macrophage polarization is upregulated in deep vein thrombosis and contributes to the upregulation of adhesion molecules

Pang, Xue; Wang, Yutao; Liu, Ming

doi:10.1016/j.humimm.2019.05.001

Cited by 9 publications

(15 citation statements)

References 26 publications

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“…The aged mice were therefore in a state of chronic low-grade inflammation known as inflammaging (Calder et al, 2017) which is consistent with previous findings (Pedersen and Bruunsgaard, 2003;Sikora et al, 2014). All of these pro-inflammatory cytokines in turn lead to the activation of endothelial cell adhesion molecules (ECAMs), such as VCAM-1 and ICAM-1, which were reported to regulate monocytes/macrophages recruitment (Pang et al, 2019). Macrophages are well known as innate immune cells and are a key player of AS because it mediates lipoprotein internalization and cytokine production that leads to localized inflammation and plaque growth (Zhou et al, 2015).…”

Section: Discussionsupporting

confidence: 89%

The Role of Intestinal Dysbacteriosis Induced Arachidonic Acid Metabolism Disorder in Inflammaging in Atherosclerosis

Sun

Zeng

et al. 2021

Front. Cell. Infect. Microbiol.

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BackgroundAging induced chronic systemic inflammatory response is an important risk factor for atherosclerosis (AS) development; however, the detailed mechanism is yet to be elucidated.ObjectiveTo explore the underlying mechanism of how aging aggravates AS advancement.MethodsA young (five-week-old, YM) and aged group (32-week-old, OM) male apoE-/- mice with a high fat diet were used as models, and age-matched male wild-type C57BL/6J (WT) mice were used as controls. AS lesion size, serum lipid profile, cytokines, and gut microbiota-derived LPS were analyzed after 32 weeks of diet intervention. A correlation analysis between the 16S rRNA sequencing of the feces and serum metabolomics profiles was applied to examine the effect of their interactions on AS.ResultsApoE-/- mice developed severe atherosclerosis and inflammation in the aorta compared to the WT groups, and aged apoE-/- mice suffered from a more severe AS lesion than their younger counterparts and had low-grade systemic inflammation. Furthermore, increased levels of serum LPS, decreased levels of SCFAs production, as well as dysfunction of the ileal mucosal barrier were detected in aged mice compared with their younger counterparts. There were significant differences in the intestinal flora composition among the four groups, and harmful bacteria such as Lachnospiraceae_FCS020, Ruminococcaceae_UCG-009, Acetatifactor, Lachnoclostridium and Lactobacillus_gasseri were significantly increased in the aged apoE-/- mice compared with the other groups. Concurrently, metabolomics profiling revealed that components involved in the arachidonic acid (AA) metabolic pathway such as 20-HETE, PGF2α, arachidonic acid, and LTB4 were significantly higher in the aged AS group than in the other groups. This suggested that metabolic abnormalities and disorders of intestinal flora occurred in AS mice.ConclusionsAging not only altered the gut microbiome community but also substantially disturbed metabolic conditions. Our results confirm that AA metabolism is associated with the imbalance of the intestinal flora in the AS lesions of aged mice. These findings may offer new insights regarding the role of gut flora disorders and its consequent metabolite changed in inflammaging during AS development.

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Section: Discussionsupporting

confidence: 89%

The Role of Intestinal Dysbacteriosis Induced Arachidonic Acid Metabolism Disorder in Inflammaging in Atherosclerosis

Sun

Zeng

et al. 2021

Front. Cell. Infect. Microbiol.

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“…The mRNA expression levels of adhesion molecules were higher in HUVECs and EA.hy926 cells incubated with M1-like media compared with HUVECs or EA.hy926 incubated with M2-like media ( Figure 4 and Supplementary Figures 3A, B ), except for VCAM1 expression in HUVECs incubated for 24 h with media, which was not different in HUVECs incubated with M1-like macrophage media compared with HUVECs incubated with M2-like macrophage media ( Supplementary Figure 3A ). This is consistent with a study in which endothelial adhesion molecule expression in ECs was shown to be more strongly induced by M1-like macrophages than M2-like macrophages ( 35 ). Interestingly, ICAM1 mRNA expression was significantly higher in EA.hy926 cells incubated for 24 h with unpolarized cyH medium, compared with EA.hy926 cells incubated for 24 h with unpolarized N or unpolarized chH media ( Figure 4A ).…”

Section: Resultssupporting

confidence: 93%

“…ICAM1 expression and protein abundance in ECs and VCAM1 and E-Selectin expression in ECs were mostly induced by M1-like macrophages and were least induced by M2-like macrophages ( Figures 4 , 5 and Supplementary Figures 3–5 ). This is consistent with a previous study showing that M1-like macrophages were more potent than M2-like macrophages to induce adhesion molecule expression in ECs ( 35 ). cyH enhanced the ability of each macrophage type to induce ICAM1 mRNA expression in HUVECs ( Figure 4B ).…”

Section: Discussionsupporting

confidence: 94%

The impact of macrophages on endothelial cells is potentiated by cycling hypoxia: Enhanced tumor inflammation and metastasis

Delprat

Huart²,

Féron³

et al. 2022

Front. Oncol.

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Cycling hypoxia (cyH), neo-angiogenesis, and tumor-associated macrophages are key features of the tumor microenvironment. In this study, we demonstrate that cyH potentiates the induction by unpolarized and M1-like macrophages of endothelial inflammatory phenotype and adhesiveness for monocytes and cancer cells. This process triggers a positive feedback loop sustaining tumor inflammation. This work opens the door for innovative therapeutic strategies to treat tumor inflammation and metastasis.In cancers, the interaction between macrophages and endothelial cells (ECs) regulates tumor inflammation and metastasis. These cells are both affected by cycling hypoxia (cyH), also called intermittent hypoxia, a feature of the tumor microenvironment. cyH is also known to favor tumor inflammation and metastasis. Nonetheless, the potential impact of cyH on the dialog between macrophages and ECs is still unknown. In this work, the effects of unpolarized, M1-like, and M2-like macrophages exposed to normoxia, chronic hypoxia (chH), and cyH on endothelial adhesion molecule expression, pro-inflammatory gene expression, and EC adhesiveness for monocytes and cancer cells were investigated. cyH increased the ability of unpolarized and M1-like macrophages to induce EC inflammation and to increase the expression of the EC endothelial adhesion molecule ICAM1, respectively. Unpolarized, M1-like, and M2-like macrophages were all able to promote EC adhesive properties toward cancer cells. Furthermore, the ability of macrophages (mostly M1-like) to shift EC phenotype toward one allowing cancer cell and monocyte adhesion onto ECs was potentiated by cyH. These effects were specific to cyH because they were not observed with chH. Together, these results show that cyH amplifies the effects of macrophages on ECs, which may promote tumor inflammation and metastasis.

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“…Subpopulations of monocytes (originally found in the blood and lymph nodes, but not in the lung, thymus, and breast milk) can rapidly cocoon themselves with fibrin deposits [91], and crosslink that fibrin by secreting Factor XIIIa, a function with pathologic implications ranging from skin wound healing [92] to lung cancer [93]. In the context of pathologic DVT in human patients, there is a polarization toward pro-inflammatory Mo/MΦ as sampled from the blood [94]. These pro-inflammatory human Mo/MΦ cells are characterized by greater IL6, TNFα, and cellular adhesion markers (such as ICAM-1) expression.…”

Section: Monocyte-derived Macrophages and Thrombus Resolutionmentioning

confidence: 99%

“…Thrombus resolution also involves endothelial cells, which assume many roles within the developing thrombus, similar to macrophages. Some of the effects of proteins secreted by endothelial cells can be understood by their linkage to the aforementioned parts of the immune system, such as ICAM-1 which is also expressed by PMNs [71] and pro-inflammatory Mo/MΦ cells [94], and Vascular Endothelial Growth Factor (VEGF) which triggers pro-resolving Mo/MΦ activation [89,101]. As noted above, endothelial cells can act as intermediaries between mast cells and infiltrating immune cells [141].…”

Section: Endothelial Cellsmentioning

confidence: 99%

Resolution of Deep Venous Thrombosis: Proposed Immune Paradigms

Nicklas

Gordon

Henke

2020

IJMS

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Venous thromboembolism (VTE) is a pathology encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE) associated with high morbidity and mortality. Because patients often present after a thrombus has already formed, the mechanisms that drive DVT resolution are being investigated in search of treatment. Herein, we review the current literature, including the molecular mechanisms of fibrinolysis and collagenolysis, as well as the critical cellular roles of macrophages, neutrophils, and endothelial cells. We propose two general models for the operation of the immune system in the context of venous thrombosis. In early thrombus resolution, neutrophil influx stabilizes the tissue through NETosis. Meanwhile, macrophages and intact neutrophils recognize the extracellular DNA by the TLR9 receptor and induce fibrosis, a complimentary stabilization method. At later stages of resolution, pro-inflammatory macrophages police the thrombus for pathogens, a role supported by both T-cells and mast cells. Once they verify sterility, these macrophages transform into their pro-resolving phenotype. Endothelial cells both coat the stabilized thrombus, a necessary early step, and can undergo an endothelial-mesenchymal transition, which impedes DVT resolution. Several of these interactions hold promise for future therapy. already progressed past the point of anticoagulant efficacy [12,13]. Thus, there is potential clinical utility in investigating and controlling the process by which DVTs resolve in order to provide better care to these later-stage patients, with less bleeding risk. Overview of Venous Thrombus Development in HumansThe time sequence of DVT development and resolution was correctly suggested as early as 1962, based on empirical stains that detected changes in the nanoscopic roughness of clotted material [14]. As Lendrum et. al. remarked, "we consider that the intracytoplasmic granules, which we think are engulfed fibrin, seen in pulmonary phagocytes and in the endothelium of arteries and veins containing thrombus, are better shown by this (methyl-scarlet-blue) method than by any of the others." In fresh clot (whether in deep veins or in diabetic kidneys), platelets and erythrocytes are initially linked in a fine mesh yielding a relatively smooth surface (stage 1). A mat of the medium-textured fibrin replaces the initial thrombus (stage 2), which is gradually replaced by much coarser collagen (stage 3). This staging of clot development quickly became the basis of a pathological guide to grade thrombi [15]. The current three-stage refinement of the DVT grading scheme indicates that the turnover of erythrocyte-rich to fibrin-rich clot in humans is complete approximately seven days after the initial thrombotic event [16], whereas fibrin deposition commences after one day [17]. Various leukocytes, initially neutrophils and later macrophages, are believed to control this progression of DVTs development from a mass of erythrocytes, to fibrin, and finally to collagen [18]. Infiltrating T-lymphocytes and macrophages conta...

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M1-macrophage polarization is upregulated in deep vein thrombosis and contributes to the upregulation of adhesion molecules

Cited by 9 publications

References 26 publications

The Role of Intestinal Dysbacteriosis Induced Arachidonic Acid Metabolism Disorder in Inflammaging in Atherosclerosis

The Role of Intestinal Dysbacteriosis Induced Arachidonic Acid Metabolism Disorder in Inflammaging in Atherosclerosis

The impact of macrophages on endothelial cells is potentiated by cycling hypoxia: Enhanced tumor inflammation and metastasis

Resolution of Deep Venous Thrombosis: Proposed Immune Paradigms

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