Macrophage and Multinucleated Giant Cell Classification

Abstract

The purpose of this chapter is to provide an overview of macrophage subtype and multinucleated giant cell classification with a specific discussion of their role(s) in response to particulates and other foreign bodies. Topics covered for the different subtypes include the following: environmental factors involved in their generation, functional characterization, disease associations, and interactions with particulates. This chapter is separated into three major parts. The first portion describes the normal structure and functions of the macrophage. Second, the currently published macrophage subsets are outlined. The classifications included in the discussion are based on function ("M" polarization) rather than anatomical position (tissue-specific macrophages -Kupffer cells, alveolar macrophages, etc.). As shown in Fig. 1.1, the ontogeny of the various types of macrophages being discussed in this chapter depends on the pathway of activation. The third major section focuses on multinucleated giant cells, which are formed by fusion of individual macrophages. The ontogeny of each subset will be discussed and the current literature regarding particulate/foreign-body interaction will be reviewed.

Renal Macrophages and Multinucleated Giant Cells: Ferrymen of the River Styx?

“…Those with a coin payment placed in their mouths during "proper" burials were allowed to embark, where the longer their passage, the deeper their delivery into Hades (1). A hypothesis is proposed here (Figure 1), founded on 70 years of previously published research on human and rodent models, that macrophages and MGCs serve in a role similar to that of Charon, in that they engulf early-stage biomineralization crystals (departed souls on the ferry) and transport them through the interstitium (the River Styx) to the papilla (2,3). If correct, in nonstone formers the crystals would completely dissolve during this transport process, whereas in stone formers the crystals would accumulate and eventually penetrate the papillary epithelia to form Randall's plaque at the margin of the calyx (the suffering of Hades; Figure 1).…”

“…These crystals, some of which bind to epithelial cell receptors, could trigger both signal transduction and a proinflammatory response that includes: ( 1 ) production of reactive oxygen species (12), ( 2 ) endocytosis (15), and ( 3 ) transport of the HAP, COD, and COM crystals through the epithelium and across the basement membrane, dislodging them into the interstitium (7,11). In response to this proinflammatory signaling cascade, blood-derived monocytes differentiate into induced macrophages (11) via 1 β and IL-13 cytokine signaling pathways in the interstitium (stage 4; Figure 1) (2,16). In both nonstone formers and stone formers, another subset of renal epithelial cells produces membranous vesicles in response to increased reactive oxygen species signaling (12).…”

The role of sex in particle‐induced inflammation and injury

“…Briefly, these phenotypes include: M1's, Th1 response and cell-mediated killing; M2a's, Th2 response, and IgE production; M2b's, Th2 response, and IgG; M2c's, anti-inflammatory, and tissue remodeling. For a more in-depth review, please refer to one of the following reviews (Martinez & Gordon, 2014;Trout, Jessop, & Migliaccio, 2016). Interestingly, AMs have been reported to adopt an M2a-like phenotype following oropharyngeal aspiration of MWCNTs in male C57BL/6 mice (female mice were not used in this study; Dong & Ma, 2018).…”