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Myeloid Cell Turnover and Clearance

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  • Authors: William J. Janssen1, Donna L. Bratton2, Claudia V. Jakubzick3, Peter M. Henson4
  • Editor: Siamon Gordon5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Departments of Pediatrics and Medicine, National Jewish Health, Denver; Departments of Immunology, Medicine, and Pediatrics, University of Colorado, Denver, Denver, CO 80231; 2: Departments of Pediatrics and Medicine, National Jewish Health, Denver; Departments of Immunology, Medicine, and Pediatrics, University of Colorado, Denver, Denver, CO 80231; 3: Departments of Pediatrics and Medicine, National Jewish Health, Denver; Departments of Immunology, Medicine, and Pediatrics, University of Colorado, Denver, Denver, CO 80231; 4: Departments of Pediatrics and Medicine, National Jewish Health, Denver; Departments of Immunology, Medicine, and Pediatrics, University of Colorado, Denver, Denver, CO 80231; 5: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0005-2015
  • Received 27 April 2015 Accepted 21 September 2016 Published 11 November 2016
  • Peter M. Henson, hensonp@njhealth.org
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  • Abstract:

    Given the dual and intrinsically contradictory roles of myeloid cells in both protective and yet also damaging effects of inflammatory and immunological processes, we suggest that it is important to consider the mechanisms and circumstances by which these cells are removed, either in the normal unchallenged state or during inflammation or disease. In this essay we address these subjects from a conceptual perspective, focusing as examples on four main myeloid cell types (neutrophils, monocytes, macrophages, and myeloid dendritic cells) and their clearance from the circulation or from naive and inflamed tissues. While the primary clearance process appears to involve endocytic uptake into macrophages, various tissue cell types can also recognize and remove dying cells, though their overall quantitative contribution is unclear. In fact, surprisingly, given the wealth of study in this area over the last 30 years, our conclusion is that we are still challenged with a substantial lack of mechanistic and regulatory understanding of when, how, and by what mechanisms migratory myeloid cells come to die and are recognized as needing to be removed, and indeed the precise processes of uptake of either the intact or fragmented cells. This reflects the extreme complexity and inherent redundancy of the clearance processes and argues for substantial investigative effort in this arena. In addition, it leads us to a sense that approaches to significant therapeutic modulation of selective myeloid clearance are still a long way off.

  • Citation: Janssen W, Bratton D, Jakubzick C, Henson P. 2016. Myeloid Cell Turnover and Clearance. Microbiol Spectrum 4(6):MCHD-0005-2015. doi:10.1128/microbiolspec.MCHD-0005-2015.

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2016-11-11
2017-03-26

Abstract:

Given the dual and intrinsically contradictory roles of myeloid cells in both protective and yet also damaging effects of inflammatory and immunological processes, we suggest that it is important to consider the mechanisms and circumstances by which these cells are removed, either in the normal unchallenged state or during inflammation or disease. In this essay we address these subjects from a conceptual perspective, focusing as examples on four main myeloid cell types (neutrophils, monocytes, macrophages, and myeloid dendritic cells) and their clearance from the circulation or from naive and inflamed tissues. While the primary clearance process appears to involve endocytic uptake into macrophages, various tissue cell types can also recognize and remove dying cells, though their overall quantitative contribution is unclear. In fact, surprisingly, given the wealth of study in this area over the last 30 years, our conclusion is that we are still challenged with a substantial lack of mechanistic and regulatory understanding of when, how, and by what mechanisms migratory myeloid cells come to die and are recognized as needing to be removed, and indeed the precise processes of uptake of either the intact or fragmented cells. This reflects the extreme complexity and inherent redundancy of the clearance processes and argues for substantial investigative effort in this arena. In addition, it leads us to a sense that approaches to significant therapeutic modulation of selective myeloid clearance are still a long way off.

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Figures

Image of FIGURE 1
FIGURE 1

Mechanisms for recognition and uptake of apoptotic cells. Changes on the apoptotic cell surface, including exposure of PS and other normally internally located molecules, are recognized by surface receptors on the phagocyte, leading to tethering of the apoptotic cell and transduction of uptake signals. Bridge molecules (opsonins) in the environment or produced by the phagocyte may also recognize the apoptotic surface changes and also a different set of receptors on the phagocyte to initiate tethering and/or signaling. These processes are significantly redundant and also highly regulated by enhancing or inhibitory stimuli. Viable cells may also avoid removal by expressing “don’t eat me” stimuli that block the recognition and/or uptake processes.

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0005-2015
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Image of FIGURE 2
FIGURE 2

Uptake of apoptotic neutrophils by a macrophage in the alveolar air space during resolution of inflammation in the lung.

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0005-2015
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Image of FIGURE 3
FIGURE 3

Time course of a standardized acute inflammatory response in the lung, showing accumulation and removal of neutrophils and monocyte/macrophages. The resident alveolar macrophages persist throughout the inflammation and do not substantially change in numbers. Some of the recruited Ly6C monocytes mature into macrophages (and DCs), and some remain as monocytes. The macrophages undergo a variety of programming changes during the course of the inflammation, participating in first its initiation and then its resolution. The monocytes and macrophages are cleared as the inflammation wanes, mostly by undergoing PCD and engulfment, though some of the monocytes migrate to the local lymph nodes and, at this site, some of the cells may also be cleared physically up the airways by the mucociliary escalator.

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0005-2015
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