The ultrastructure of multinucleate giant cells

Abstract

A survey of the available ultrastructural data on physiologically and pathologically occurring and virally-induced multinucleate giant cells (MNGCs) is presented. Emphasis is initially placed upon the bone osteoclast, the skeletal muscle myotube and the placental syncytiotrophoblast. The widespread occurrence of MNGCs in a range of pathological situations is discussed, with emphasis upon the broad involvement of the macrophage in inflammatory responses. Many viruses produce cell fusion in vivo and in vitro when cell cultures are infected. Several examples are given. A clear distinction is drawn between viral fusion from "without" and viral fusion from "within" the cell. The cytopathic effect (CPE) of the animal and human retroviruses is discussed in considerable detail. The in vivo and in vitro formation of lymphocytic and macrophage MNGCs by HIV-1 is given extensive coverage. The possible significance of the presence of brain MNGCs of macrophage/ microglial origin as a cellular feature of AIDS dementia is discussed. A new hypothesis is advanced relating to the possible role of endogenous C-type retrovirus in the physiological fusion of the invasive placental cytotrophoblasts to create the syncytiotrophoblast. The evolutionary and developmental significance of such an event in relation to the evolution of the placental mammals is discussed. The possible importance of MNGC formation in the depletion of the CD4 ÷ population of T-lymphocytes in vivo in the clinical progression of the AIDS-related complex and AIDS is related to the potent fusogenic effect of HIV-I when cell cultures are infected.

Time Course of Gag Protein Assembly in HIV-1-Infected Cells: A Study by Immunoelectron Microscopy

“…4a). The medium used for low-temperature embedding does not visualize vesicular structures well enough to enable their identification, but as a whole our observations are in line with reports by Grief et al (1991) and others (reviewed in Harris, 1993), which showed that the major producers of the virus were multinuclear cells, while single cells were mostly free of signs of assembly or budding. No immunolabeling for Gag was done in the above papers, limiting our ability to make direct comparisons.…”

Placental endogenous retrovirus (ERV): structural, functional, and evolutionary significance

“…Throughout the 1970s, C-type retrovirus(es) were detected by EM in the normal placenta of baboons and a number of other primates, cats, mice, and guinea pigs 6 (see Daniel and Chilton 10 for review), as well as in humans. 11,12 These data were supported by the isolation of retroviral particles from the baboon and rhesus monkey.…”

“…The role of apoptosis, if any, in the ultimate degeneration of placental tissue remains to be firmly established. Ultrastructural indications from the formation of clustered nuclei containing condensed chromatin (nuclear/syncytial knots) in human placental syncytiotrophoblast at term 6,72 (even more dramatically under conditions of rhesus incompatibility), is characteristic of apoptosis. The claim that apoptosis can be identified in human trophoblastic cells by in situ nick end labeling of fragmented DNA 73 provides evidence that controlled cell death does play a role in the terminal differentiation of the placenta.…”

“…In all mammals with a syncytiotrophoblast it is now accepted that cell fusion events occur, whereby the outermost layer of placental cytotrophoblasts, with well-organized desmosomal/gap junctions between them, undergo cell-cell fusion to create the single-cell-thick syncytiotrophoblast barrier between the maternal and fetal circulations. 6,72,78,79 Gap junctions remain between the syncytiotrophoblast and adjacent unfused cytotrophoblasts, and gap junction remnants can be detected within the syncytiotrophoblast. 6,72 Indeed, the expression pattern of connexins within the gap junctions of the trophoblast has been related to placental differentiation and control of myometrial invasion.…”

“…6,72,78,79 Gap junctions remain between the syncytiotrophoblast and adjacent unfused cytotrophoblasts, and gap junction remnants can be detected within the syncytiotrophoblast. 6,72 Indeed, the expression pattern of connexins within the gap junctions of the trophoblast has been related to placental differentiation and control of myometrial invasion. 80 Interestingly, the trophoblast/syncytiotrophoblast alone has been considered to represent an incomplete barrier to transplacental exchange, 71 since the existence of welldefined cadherin arrays of the zonula adherans and discontinuous zonula occludens/tight junctions between the endothelial cells of the adjacent fetal capillaries may also contribute to the restriction of the transplacental exchange of macromolecules.…”