Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites

By F. Swirski, Matthias Nahrendorf, Martin Etzrodt, M. Wildgruber, V. Cortez-Retamozo, Peter R. Panizzi, Jose-Luiz Figueiredo, R. Kohler, A. Chudnovskiy, P. Waterman and 5 more. Science, 2009

2,240 citations recorded by the source corpus.

Monitoring Monocyte Reservoirs Monocytes are cells of the immune system that are recruited to sites of tissue injury and inflammation where they help to resolve the infection and are important for tissue repair. The bone marrow and blood are believed to be the primary reservoirs from which monocytes are mobilized after injury. Swirski et al. (p. 612; see the Perspective by Jia and Pamer) now demonstrate that the spleen also serves as a critical reservoir of monocytes that are recruited during ischemic myocardial injury. Monocytes in the spleen are very similar in phenotype to blood-derived monocytes and are mobilized to the injured heart, where they represent a large fraction of the total monocytes that are recruited. The chemoattractant, angiotensin II, is required for optimal monocyte mobilization from the spleen and emigration into injured tissue. A rapid deployment force of immune cells is identified in the spleen that is important for resolving inflammation. A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c56b87e867cfc8c9725ce3b31eb4f4bc7116ee70

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Citations in the corpus

Macrophage heterogeneity in tissues: phenotypic diversity and functions (2014, background): “(80) have demonstrated that undifferentiated monocytes reside in the spleen, outnumber their equivalents in circulation, and are recruited from spleen to sites of inflammation such as myocardial infarction.”
Origin and Functions of Tissue Macrophages (2014, result): “…~25% of skin macrophages were not replaced, even after 1 year posttransplant, suggesting that some human skin resident macrophages might persist independently of circulating monocyte input, which is similar to what has been observed in mice (Jakubzick et al., 2013; Tamoutounour et al., 2013).”
Macrophage plasticity and polarization: in vivo veritas. (2012, neutral): “(44), suggesting that this is a general feature of the natural history of repair processes.”
Imaging macrophages with nanoparticles. (2014, methodology): “For these reasons, macrophage imaging with nanoparticles is attractive and may be used to (1) identify high-risk patients and vascular regions, (2) predict risk of plaque rupture and (3) evaluate therapies.”
Origins of tumor-associated macrophages and neutrophils (2012, methodology): “However, the spleen is a multicellular organ, capable of accommodating many major functions for the host, including immune protection against pathogens as well as orchestration of healing responses (17).”
Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis (2012, positive): “To exclude this possibility, we isolated CX 3 CR1 GFP/+ Ly6C + monocytes from the splenic reservoir (Swirski et al., 2009) and grafted them into congenic WT mice (Supplemental Fig.”