Monocyte and macrophage heterogeneity

Gordon, Siamon; Taylor, Philip Russel

doi:10.1038/nri1733

Cited by 4,489 publications

(4,203 citation statements)

References 90 publications

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“…However, there is accumulating evidence that neutrophils are the first wave of leukocytes that pave the way for the succeeding monocytes, which eventually differentiate into macrophages and dendritic cells. 18 Interestingly, we observed that the meninges covering the ischemic area seem to be the exclusive point of entry for the aforementioned first wave of leukocytes. Mast cells residing in the meninges have been discussed as important factor for the early influx of neutrophils, 19,20 which in turn attracted monocytes by releasing 'find me' and 'eat me' signals.…”

Section: Discussionmentioning

confidence: 72%

Sterile Inflammation after Permanent Distal MCA Occlusion in Hypertensive Rats

Möller

Boltze²,

Pösel

et al. 2013

J Cereb Blood Flow Metab

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The pathophysiology of stroke is governed by immune reactions within and remote from the injured brain. Hypertension, a major cause and comorbidity of stroke, entails systemic vascular inflammation and may influence poststroke immune responses. This aspect is, however, underestimated in previous studies. Here we aimed to delineate the sequence of cellular inflammation after stroke in spontaneously hypertensive (SH) rats. Spontaneously hypertensive rats were subjected to permanent middle cerebral artery occlusion and killed after 1 or 4 days. Immune cells of the peripheral blood and those which have infiltrated the injured brain were identified and quantified by flow cytometry. The spatial distribution of myeloid cells and T lymphocytes, and the infarct volume were assessed by histology. We observed a concerted infiltration of immune cells into the ischemic brain of SH rats. At day 1, primarily neutrophils, monocytes, macrophages, and myeloid dendritic cells entered the brain, whereas the situation at day 4 was dominated by microglia, macrophages, lymphatic dendritic cells, and T cells. Postischemic inflammation did not cause secondary tissue damage during the subacute stage of experimental stroke in SH rats. Considering the intrinsic vascular pathology of SH rats, our study validates this strain for further translational research in poststroke inflammation.

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Section: Discussionmentioning

confidence: 72%

Sterile Inflammation after Permanent Distal MCA Occlusion in Hypertensive Rats

Möller

Boltze²,

Pösel

et al. 2013

J Cereb Blood Flow Metab

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“…Conversely, the Ly6C low subsets lack Ccr2 but express high levels of Cx3cr1. The expression of Ccr2 and the capacity to migrate toward the Ccr2 ligand CC‐chemokine ligand 2 (CCL2) is consistent with the role of this chemokine and its receptor in the recruitment of monocytes to inflammatory lesions, so the subset of monocytes that expresses Ccr2 is known as the ‘inflammatory’ subset (Gordon and Taylor, 2005). Within inflamed tissues, Ccr2 + Cx3cr1 low Ly6C + monocytes differentiate into macrophages (blood‐derived macrophages).…”

Section: Introductionmentioning

confidence: 76%

“…Within inflamed tissues, Ccr2 + Cx3cr1 low Ly6C + monocytes differentiate into macrophages (blood‐derived macrophages). In the absence of inflammation, Ccr2 ‐ Cx3cr1 hi Ly6C ‐ monocytes are postulated to enter the tissues and replenish the ‘tissue‐resident’ macrophage, known as resident microglia in the brain (Gordon and Taylor, 2005). To distinguish resident microglia from blood‐derived macrophages in the brain after injury, Saederup et al generated red fluorescent protein (RFP)‐Ccr2 knock‐in mice (Ccr2 RFP/RFP ) and crossed them with green fluorescent protein (GFP)‐Cx3cr1 mice (Cx3cr1 GFP/GFP ) (Saederup et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Resident microglia, rather than blood‐derived macrophages, contribute to the earlier and more pronounced inflammatory reaction in the immature compared with the adult hippocampus after hypoxia‐ischemia

Umekawa

Osman

Han

et al. 2015

Glia

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The mechanisms of neuronal injury after hypoxia–ischemia (HI) are different in the immature and the adult brain, but microglia activation has not been compared. The purpose of this study was to phenotype resident microglia and blood‐derived macrophages in the hippocampus after HI in neonatal (postnatal day 9, P9) or adult (3 months of age, 3mo) mice. Unilateral brain injury after HI was induced in Cx3cr1GFP/+Ccr2RFP/+ male mice on P9 (n = 34) or at 3mo (n = 53) using the Vannucci model. Resident microglia (Cx3cr1‐GFP+) proliferated and were activated earlier after HI in the P9 (1–3 days) than that in the 3mo hippocampus, but remained longer in the adult brain (3–7 days). Blood‐derived macrophages (Ccr2‐RFP+) peaked 3 days after HI in both immature (P9) and adult (3mo) hippocampi but were twice as frequent in adult brains, 41% vs. 21% of all microglia/macrophages. CCL2 expression was three times higher in the P9 hippocampi, indicating that the proinflammatory response was more pronounced in the immature brain after HI. This corresponded well with the higher numbers of galectin‐3‐positive resident microglia in the P9 hippocampi, but did not correlate with CD16/32‐ or CD206‐positive resident microglia or blood‐derived macrophages. In conclusion, resident microglia, rather than infiltrating blood‐derived macrophages, proliferate and are activated earlier in the immature than in the adult brain, but remain increased longer in the adult brain. The inflammatory response is more pronounced in the immature brain, and this correlate well with galectin‐3 expression in resident microglia. GLIA 2015;63:2220–2230

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“…They also fulfill homeostatic functions including tissue remodeling and the resolution of tissue damage. Heterogeneity of the macrophage lineage has long been recognized (Gordon & Taylor, 2005), and they have different functional roles depending on their tissue location and the inflammatory environment that drives their activation (Davies et al ., 2013). In this context, macrophage activation has been conventionally categorized into pro‐inflammatory M1 macrophages, induced by IFN‐γ and toll‐like receptor (TLR) ligands, and the alternatively activated anti‐inflammatory M2 macrophages, induced by IL‐4/IL‐13 (Biswas & Mantovani, 2010; Gordon & Martinez, 2010).…”

Section: Cellular Senescence and Immune Cell Fate Decisionmentioning

confidence: 99%

Cellular senescence impact on immune cell fate and function

et al. 2016

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SummaryCellular senescence occurs not only in cultured fibroblasts, but also in undifferentiated and specialized cells from various tissues of all ages, in vitro and in vivo. Here, we review recent findings on the role of cellular senescence in immune cell fate decisions in macrophage polarization, natural killer cell phenotype, and following T‐lymphocyte activation. We also introduce the involvement of the onset of cellular senescence in some immune responses including T‐helper lymphocyte‐dependent tissue homeostatic functions and T‐regulatory cell‐dependent suppressive mechanisms. Altogether, these data propose that cellular senescence plays a wide‐reaching role as a homeostatic orchestrator.

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Monocyte and macrophage heterogeneity

Cited by 4,489 publications

References 90 publications

Sterile Inflammation after Permanent Distal MCA Occlusion in Hypertensive Rats

Sterile Inflammation after Permanent Distal MCA Occlusion in Hypertensive Rats

Resident microglia, rather than blood‐derived macrophages, contribute to the earlier and more pronounced inflammatory reaction in the immature compared with the adult hippocampus after hypoxia‐ischemia

Cellular senescence impact on immune cell fate and function

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