Intercellular Adhesion Molecule 1 Functions as an Efferocytosis Receptor in Inflammatory Macrophages

Wiesolek, Hannah L.; Bui, Triet M.; Lee, Joseph; Dalal, Prarthana; Finkielsztein, Ariel; Batra, Ayush; Thorp, Edward B.; Sumagin, Ronen

doi:10.1016/j.ajpath.2019.12.006

Cited by 56 publications

(55 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…31 In macrophages, IFN and LPS stimulation induced a robust up-regulation of ICAM-1 compared to relatively small effect of TNF or IL-1 . 32 ICAM-1 expression was also shown to be regulated by microRNA activity. MiR-141 in ECs was found to down-regulate ICAM-1, thus decreasing leukocyte adhesion and attenuating myocardial ischemia-reperfusion injury.…”

Section: Icam-1 Expression and Function In Inflammationmentioning

confidence: 97%

“…51 We recently demonstrated that ICAM-1 expression was highly induced in inflammatory macrophages, where it served as a phagocytic receptor and mediated binding of macrophages and apoptotic cells, facilitating apoptotic clearance. 32 Finally, ICAM-1 expression was also induced on activated murine and human PMNs. In murine PMNs, LPS-driven induction of ICAM-1 expression was associated with enhanced reactive oxygen species (ROS) generation and improved phagocytoses.…”

Section: Icam-1 Regulates Leukocyte Trafficking and Effector Functionmentioning

confidence: 98%

“…109,110 We found that ICAM-1 expressed by inflammatory macrophages played an important role in efferocytosis (clearance of apoptotic/dead cells) of immune and epithelial cells. 32 Efferocytosis also leads to cellular reprogramming in newly recruited inflammatory macrophages, which in turn suppress inflammatory response and increase production of pro-resolution cytokines, including IL-10, TGF-, and PGE2. 111,112 Furthermore, ICAM-1 was found to directly impact macrophage polarization and promote the pro-repair phenotype by positively modulating miR-124 expression.…”

Section: Icam-1 and Immune Cell Effector Function In Resolution Of Inmentioning

confidence: 99%

See 2 more Smart Citations

ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis

Bui

Wiesolek

Sumagin

2020

Journal of Leukocyte Biology

Self Cite

519

318

View full text Add to dashboard Cite

ICAM‐1 is a cell surface glycoprotein and an adhesion receptor that is best known for regulating leukocyte recruitment from circulation to sites of inflammation. However, in addition to vascular endothelial cells, ICAM‐1 expression is also robustly induced on epithelial and immune cells in response to inflammatory stimulation. Importantly, ICAM‐1 serves as a biosensor to transduce outside‐in‐signaling via association of its cytoplasmic domain with the actin cytoskeleton following ligand engagement of the extracellular domain. Thus, ICAM‐1 has emerged as a master regulator of many essential cellular functions both at the onset and at the resolution of pathologic conditions. Because the role of ICAM‐1 in driving inflammatory responses is well recognized, this review will mainly focus on newly emerging roles of ICAM‐1 in epithelial injury‐resolution responses, as well as immune cell effector function in inflammation and tumorigenesis. ICAM‐1 has been of clinical and therapeutic interest for some time now; however, several attempts at inhibiting its function to improve injury resolution have failed. Perhaps, better understanding of its beneficial roles in resolution of inflammation or its emerging function in tumorigenesis will spark new interest in revisiting the clinical value of ICAM‐1 as a potential therapeutic target.

show abstract

Section: Icam-1 Expression and Function In Inflammationmentioning

confidence: 97%

Section: Icam-1 Regulates Leukocyte Trafficking and Effector Functionmentioning

confidence: 98%

Section: Icam-1 and Immune Cell Effector Function In Resolution Of Inmentioning

confidence: 99%

See 1 more Smart Citation

ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis

Bui

Wiesolek

Sumagin

2020

Journal of Leukocyte Biology

Self Cite

519

318

View full text Add to dashboard Cite

show abstract

“…Although several studies have reported on the presence of ICAM-1 on macrophage[ 27 , 29 ], little is known about the function of macrophage ICAM-1 under LPS stimulation. To investigate the role of LPS in ICAM-1 regulation, we compared the expression of ICAM-1 in BMDM after stimulating with or without LPS (1 μg/ml).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, inflammatory factors, such as TNF-ɑ, LPS, stimulate ICAM-1 expression in mouse macrophages [ 29 ]. Although several studies have reported that the relationship between ICAM-1 and macrophage polarization [ 27 , 28 ], little know about others function of ICAM-1 on macrophage under LPS stimulation. In our results, the cell surface expression of ICAM-1 was increased in LPS-stimulated macrophage.…”

Section: Discussionmentioning

confidence: 99%

Macrophage ICAM-1 functions as a regulator of phagocytosis in LPS induced endotoxemia

et al. 2021

View full text Add to dashboard Cite

Objective Intracellular adhesion molecule-1 (ICAM-1), a transmembrane glycoprotein belonging to the immunoglobulin superfamily, plays a critical role in mediating cell-cell interaction and outside-in cell signaling during the immune response. ICAM-1 is expressed on the cell surface of several cell types including endothelial cells, epithelial cells, leucocytes, fibroblasts, and neutrophils. Despite ICAM-1 has been detected on macrophage, little is known about the function and mechanism of macrophage ICAM-1. Methods To investigate the role of lipopolysaccharide (LPS) in ICAM-1 regulation, both the protein and cell surface expression of ICAM-1 were measured. The phagocytosis of macrophage was evaluated by flow cytometry and Confocal microscopy. Small interfering RNA and neutralizing antibody of ICAM-1 were used to assess the effect of ICAM-1 on macrophage phagocytosis. TLR4 gene knockout mouse and cytoplasmic and mitochondrial ROS scavenger were used for the regulation of ICAM-1 expression. ROS was determined using flow cytometry. Results In this study, we reported that macrophage can be stimulated to increase both the protein and cell surface expression of ICAM-1 by LPS. Macrophage ICAM-1 expression was correlated with enhanced macrophage phagocytosis. We found that using ICAM-1 neutralizing antibody or ICAM-1 silencing to attenuate the function or expression of ICAM-1 could decrease LPS-induced macrophage phagocytosis. Furthermore, we found that knocking out of TLR4 led to inhibited cytoplasmic and mitochondrial ROS production, which in turn, attenuated ICAM-1 expression at both the protein and cell surface levels. Conclusion This study demonstrates that the mechanism of ICAM-1-mediated macrophage phagocytosis is depending on TLR4-mediated ROS production and provides significant light on macrophage ICAM-1 in endotoxemia.

show abstract

Impact of latency‐reversing agents on human macrophage physiology

Hany

Turmel

Barat

et al. 2022

Immunity Inflam & Disease

View full text Add to dashboard Cite

Introduction HIV‐1 eradication is hindered by the presence of inducible long‐lived reservoirs of latently infected cells which rapidly disseminate viral particles upon treatment interruption. Eliminating these reservoirs by the so‐called shock and kill strategy represents a crucial concept toward an HIV‐1 cure. Several molecules called latency‐reversing agents (LRAs) are under intensive investigations to reactivate virus gene expression. These studies are mainly conducted on CD4 + T cells where LRAs are well tolerated and did not induce global cellular activation. However, despite their broad spectrum, the putative impact of LRAs on other cellular reservoirs such as macrophages is still ill‐defined. Methods We investigated the impact of the protein kinase C (PKC) activator bryostatin‐1, bromodomain inhibitor JQ1 and histone deacetylase inhibitor romidepsin used either alone or in combination on human primary monocyte‐derived macrophages (MDMs). Results We demonstrate that bryostatin‐1, JQ1, and romidepsin or their combinations are not toxic at nanomolar concentrations but induce metabolic and morphologic alterations of MDMs. Bryostatin‐1 triggered the secretion of pro‐inflammatory cytokines, while JQ‐1 decreased it. Phagocytosis and endocytosis were modestly impaired upon bryostatin‐1 treatment whereas efferocytosis was markedly downregulated by romidepsin. Despite its pro‐inflammatory profile, bryostatin‐1 did not induce classically activated macrophage markers. Finally, we reveal that conditioned medium from bryostatin‐1‐treated macrophages did not potentiate its reactivation feature. Conclusions Our study reveals that LRAs can diversely impact basic physiologic features of human primary macrophages and could potentially decrease reactivation of nearby CD4 + T cells latently infected with HIV‐1. Our observations further stress the need to include different cell populations when assessing HIV‐1 cure strategies.

show abstract

Intercellular Adhesion Molecule 1 Functions as an Efferocytosis Receptor in Inflammatory Macrophages

Cited by 56 publications

References 56 publications

ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis

ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis

Macrophage ICAM-1 functions as a regulator of phagocytosis in LPS induced endotoxemia

Impact of latency‐reversing agents on human macrophage physiology

Contact Info

Product

Resources

About