Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites

Świrski, Filip K.; Nahrendorf, Matthias; Etzrodt, Martin; Wildgruber, Moritz; Cortez-Retamozo, Virna; Panizzi, Peter; Figueiredo, José-Luiz; Köhler, Rainer H.; Chudnovskiy, Aleksey; Waterman, Peter; Aikawa, Elena; Mempel, Thorsten R.; Libby, Peter; Weissleder, Ralph; Pittet, Mikaël J.

doi:10.1126/science.1175202

Cited by 1,892 publications

(1,968 citation statements)

References 27 publications

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“…86e88 A splenic reservoir of monocytes has been identified in mice, which is mobilized in response to myocardial infarction and lung adenocarcinoma. 89,90 Alternatively, emerging studies support the notion of parenchymal macrophage repopulation in tissues and not from bone marrow, which is an interesting field of future study that may, in part, account for a lack of BrdU þ CD163 macrophages in parenchymal lesions in our study. 91,92 The Presence of CD163 þ BrdU þ Macrophages in the Meninges and Choroid Plexus Underscores Differences between CNS Compartments and a Possible Route of Viral Entry into the CNS Given that we did not observe CD163 þ BrdU þ macrophages in the perivascular space and SIVE lesions, it is interesting that we observed CD163 þ BrdU þ macrophages in the meninges and choroid plexus in numbers equal to or greater than MAC387 þ BrdU þ macrophages.…”

Section: Mac387 þ Macrophages Do Not Appear To Differentiate Into Cd1supporting

confidence: 56%

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

Nowlin

Burdo

Midkiff

et al. 2015

The American Journal of Pathology

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Macrophage recruitment to the central nervous system (CNS) during AIDS pathogenesis is poorly understood. We measured the accumulation of brain perivascular (CD163 þ ) and inflammatory (MAC387 þ ) macrophages in SIV-infected monkeys. Monocyte progenitors were 5-bromo-2 0 -deoxyuridine (BrdU) labeled in bone marrow, and CNS macrophages were labeled serially with fluorescent dextrans injected into the cisterna magna. MAC387 þ macrophages accumulated in the meninges and choroid plexus in early inflammation and in the perivascular space and SIV encephalitis (SIVE) lesions late. CD163 þ macrophages accumulated in the perivascular space and SIVE lesions with late inflammation. Most of the BrdU þ cells were MAC387 þ ; however, CD163 þ BrdU þ macrophages were present in the meninges and choroid plexus with AIDS. Most (81.6% AE 1.8%) of macrophages in SIVE lesions were present in the CNS before SIVE lesion formation. There was a 2.9-fold increase in SIVp28 þ macrophages entering the CNS late compared with those entering early (P < 0.05). The rate of CD163 þ macrophage recruitment to the CNS inversely correlated with time to death (P < 0.03) and increased with SIVE. In SIVE animals, soluble CD163 correlated with CD163 þ macrophage recruitment (P Z 0.02). Most perivascular macrophages that comprise SIVE lesions and multinucleated giant cells are present in the CNS early, before SIVE lesions are formed. Most SIV-infected macrophages traffic to the CNS terminally with AIDS.

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Section: Mac387 þ Macrophages Do Not Appear To Differentiate Into Cd1supporting

confidence: 56%

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

Nowlin

Burdo

Midkiff

et al. 2015

The American Journal of Pathology

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“…In this context, it has been suggested that bone marrow monocytes are mobilized into the bloodstream by a GM-CSFdependent pathway in experimental autoimmune encephalomyelitis prior to their trafficking into the inflamed brain (40). Swirski et al (43) showed that, in response to ischemic myocardial injury, splenic monocytes are rapidly deployed to the injured site. However, despite there being significantly fewer splenic monocytes on day 5 following serum transfer in C57BL/6 mice compared with GM-CSF Ϫ/Ϫ mice, there was little change in monocyte/macrophage cell numbers in both strains during arthritis development, which was in contrast to that seen in the bone marrow.…”

Section: Discussionmentioning

confidence: 99%

“…We next determined whether a lack of GM-CSF influenced monocyte numbers in the bone marrow and/or spleen following K/BxN serum transfer, since these tissues have both been suggested to be a source of Ly-6C high blood monocytes during inflammation (33,43). Following serum transfer, there was an early slight reduction in the number of bone marrow monocytes (identified as Mac-1 high Ly-6C high [33]).…”

Section: Effect Of Gm-csf On Myeloid Cells In Cia 2345mentioning

confidence: 99%

Regulation of systemic and local myeloid cell subpopulations by bone marrow cell–derived granulocyte–macrophage colony‐stimulating factor in experimental inflammatory arthritis

Cook

Turner

Braine

et al. 2011

Arthritis & Rheumatism

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Objective. Even though there are clinical trials assessing granulocyte-macrophage colony-stimulating factor (GM-CSF) blockade in rheumatoid arthritis (RA), questions remain as to how GM-CSF acts as a proinflammatory cytokine. The aims of this study on the regulation of arthritis progression by GM-CSF were to determine the source of the GM-CSF, whether there are systemic effects, the changes in synovial tissue leukocyte populations, and the arthritis model dependence on GM-CSF.Methods. Bone marrow chimeras were used to determine the source of GM-CSF required for the development of collagen-induced arthritis (CIA). The K/BxN serum-transfer model of arthritis was tested in GM-CSF ؊/؊ mice and using anti-GM-CSF monoclonal antibodies. Cell populations from arthritic mice were assessed by differential staining and flow cytometry.Results. In the CIA model, GM-CSF produced by bone marrow-derived cells was required for arthritis development. GM-CSF blockade, while ameliorating the development of CIA, was found to have systemic effects, limiting the increase in circulating Ly-6C high monocytes and neutrophils. GM-CSF blockade led to fewer synovial macrophages (both Ly-6C high and Ly-6C low ), neutrophils, and lymphocytes. In the absence of GM-CSF, K/BxN serum-transfer arthritis initially developed normally; however, the numbers of Ly-6C high monocytes and synovial macrophages (both Ly-6C high and Ly-6C low ) were again reduced, along with the peak disease severity and maintenance.Conclusion. GM-CSF is a key player in two arthritis models, participating in interactions between hemopoietic cells, both locally and systemically, to control myeloid cell numbers as well as presumably to "activate" them. These results could be useful for the analysis of current clinical trials targeting GM-CSF in patients with RA.Granulocyte-macrophage colony-stimulating factor (GM-CSF) was initially discovered by its role in the differentiation of hemopoietic precursor cells into mature granulocytes and macrophages (1); however, it can also affect mature cell function and may be considered a proinflammatory cytokine (2-4). In this context, clinical trials are in progress testing this concept in rheumatoid arthritis (RA) (4).GM-CSF is produced in vitro by a number of different cell types following exposure to various stimuli (4-8). A so-called CSF network has been proposed in which GM-CSF and other CSFs form part of a cytokinemediated hemopoietic cell-tissue cell interaction that drives chronic inflammatory reactions, for example, in joints (9). In support of this concept, several models of disease, including arthritis (10-12), multiple sclerosis Professor Hamilton has received consulting fees from MorphoSys AG and CSL, Ltd. (less than $10,000 a year). The University of Melbourne has licensed to MorphoSys AG, Germany, patented technology relating to therapeutically targeting granulocyte-macrophage colony-stimulating factor, for which licensing fees and milestone payments have been made.

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“…Swirski et al [82] have reported that the number of monocytes in the heart following myocardial infarction exceeds the number in circulation, identifying the spleen as a reservoir of undifferentiated monocytes which are rapidly deployed after myocardial infarction [82]. The role of the spleen in cerebral ischemia has also been investigated.…”

Section: Monocytes and Monocyte-derived Macrophagesmentioning

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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Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites

Cited by 1,892 publications

References 27 publications

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

Regulation of systemic and local myeloid cell subpopulations by bone marrow cell–derived granulocyte–macrophage colony‐stimulating factor in experimental inflammatory arthritis

Microglia and Monocyte-Derived Macrophages in Stroke

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