Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata

Świrski, Filip K.; Libby, Peter; Aikawa, Elena; Alcaide, Pilar; Luscinskas, F. William; Weissleder, Ralph; Pittet, Mikaël J.

doi:10.1172/jci29950

Cited by 1,093 publications

(1,144 citation statements)

References 56 publications

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“…It has been shown that the CX3CR1 lo /Ly-6C + MO population is recruited in injured or infl amed tissues (9,13,48). Our experiments using LX-labeled circulating MOs showed that CX3CR1 lo /Ly-6C + MOs were selectively recruited rapidly after muscle injury.…”

Section: Discussionmentioning

confidence: 55%

Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis

Arnold¹,

Henry²,

Poron³

et al. 2007

J Cell Biol

514

934

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Section: Discussionmentioning

confidence: 55%

Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis

Arnold¹,

Henry²,

Poron³

et al. 2007

J Cell Biol

514

934

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“…S100A9, a protein expressed in monocytes and neutrophils but absent in resident macrophages (11,12), was used as a marker. We also investigated monocytes/macrophages positive for the Ly-6C antigen, which were recently shown to preferentially infiltrate lesions in fat-fed nondiabetic mice (15,16).…”

Section: Resultsmentioning

confidence: 99%

Type 1 diabetes promotes disruption of advanced atherosclerotic lesions in LDL receptor-deficient mice

Johansson¹,

Kramer²,

Barnhart³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Cardiovascular disease, largely because of disruption of atherosclerotic lesions, accounts for the majority of deaths in people with type 1 diabetes. Recent mouse models have provided insights into the accelerated atherosclerotic lesion initiation in diabetes, but it is unknown whether diabetes directly worsens more clinically relevant advanced lesions. We therefore used an LDL receptordeficient mouse model, in which type 1 diabetes can be induced at will, to investigate the effects of diabetes on preexisting lesions. Advanced lesions were induced by feeding mice a high-fat diet for 16 weeks before induction of diabetes. Diabetes, independently of lesion size, increased intraplaque hemorrhage and plaque disruption in the brachiocephalic artery of mice fed low-fat or high-fat diets for an additional 14 weeks. Hyperglycemia was not sufficient to induce plaque disruption. Furthermore, diabetes resulted in increased accumulation of monocytic cells positive for S100A9, a proinflammatory biomarker for cardiovascular events, and for a macrophage marker protein, without increasing lesion macrophage content. S100A9 immunoreactivity correlated with intraplaque hemorrhage. Aggressive lowering primarily of triglyceride-rich lipoproteins prevented both plaque disruption and the increased S100A9 in diabetic atherosclerotic lesions. Conversely, oleate promoted macrophage differentiation into an S100A9-positive population in vitro, thereby mimicking the effects of diabetes. Thus, diabetes increases plaque disruption, independently of effects on plaque initiation, through a mechanism that requires triglyceride-rich lipoproteins and is associated with an increased accumulation of S100A9-positive monocytic cells. These findings indicate an important link between diabetes, plaque disruption, and the innate immune system. intraplaque hemorrhage ͉ macrophage ͉ S100A9

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“…Studies also suggest that hyperlipidemia shifts mononuclear phagocytes towards proinflammatory activated phenotypes. An extreme hyperlipidemic condition generated by feeding a high fat/cholesterol diet to ApoE knockout mice induced significant monocytosis in the spleen and blood, comprised mainly of the proinflammatory Ly-6C hi subset [240]. The hyperlipidemia-induced monocytosis occurs through increased production in the bone marrow, increased survival in the periphery, and reduced conversion from Ly-6C hi to the Ly-6C lo subset [240,241].…”

Section: Hyperlipidemiamentioning

confidence: 99%

“…An extreme hyperlipidemic condition generated by feeding a high fat/cholesterol diet to ApoE knockout mice induced significant monocytosis in the spleen and blood, comprised mainly of the proinflammatory Ly-6C hi subset [240]. The hyperlipidemia-induced monocytosis occurs through increased production in the bone marrow, increased survival in the periphery, and reduced conversion from Ly-6C hi to the Ly-6C lo subset [240,241]. Ly-6C hi monocytes actively accumulate into early atherosclerotic plaques, differentiate to M1 activated macrophages, and contribute to the progression of atherosclerosis [242].…”

Section: Hyperlipidemiamentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata

Cited by 1,093 publications

References 56 publications

Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis

Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis

Type 1 diabetes promotes disruption of advanced atherosclerotic lesions in LDL receptor-deficient mice

Microglia and Monocyte-Derived Macrophages in Stroke

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