Chapter 7 : Myeloid Cell Turnover and Clearance

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Few, if any, individual cells survive throughout the life of the animal, an observation that sets up the critical concepts of cell life span, turnover, and removal and maintenance of homeostatic cell numbers. These issues are of special interest for understanding the properties of the myeloid cell lineage, which includes cells such as neutrophils, which may exhibit in the normal naive adult mammal the shortest life span of all but yet are maintained in relatively constant numbers within the circulation. However, our understanding of the underlying mechanisms for myeloid cell maintenance and removal is still substantially limited and also requires reexamination in light of new ideas about the ontogeny, characterization, and distribution of the myeloid cells in general. Accordingly, this essay will focus on the concepts and questions that, we argue, are in need of exploration, rather than providing a detailed review of what is a huge literature. By focusing on four of the myeloid-lineage cell types (neutrophils, monocytes, macrophages, and dendritic cells [DCs]), we will also be able to bring to the fore many of the key issues that characterize this set of questions.

Citation: Janssen W, Bratton D, Jakubzick C, Henson P. 2017. Myeloid Cell Turnover and Clearance, p 99-115. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0005-2015
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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.

Citation: Janssen W, Bratton D, Jakubzick C, Henson P. 2017. Myeloid Cell Turnover and Clearance, p 99-115. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0005-2015
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Figure 2

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

Citation: Janssen W, Bratton D, Jakubzick C, Henson P. 2017. Myeloid Cell Turnover and Clearance, p 99-115. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0005-2015
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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.

Citation: Janssen W, Bratton D, Jakubzick C, Henson P. 2017. Myeloid Cell Turnover and Clearance, p 99-115. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0005-2015
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