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Multinuclear giant cells derived from hematopoietic stem cells or monocyte/macrophage lineage cells are subdivided into osteoclasts, bone resorbing cells, and macrophage giant cells (MGCs) including foreign body giant cells (hereafter described as FBGCs), which are induced at the site of implanted biomaterials, tumors, chronic inflammation and an infection such as tuberculosis. The most characteristic feature of these cells is multinucleation induced by the cell–cell fusion of mononuclear cells, a phenomenon first reported over 60 years ago. To date, combinations of cytokines for osteoclastogenesis or MGC formation have been identified, and osteoclasts and MGCs can be generated in the presence of specific combinations of cytokines in vitro. This makes it possible to isolate specific molecules for cell–cell fusion or to analyze the mechanisms and roles of multinucleation in osteoclasts and MGCs. Recent studies have accumulated data on molecules essential for the cell–cell fusion of osteoclasts and MGCs, and on the role of cell–cell fusion of osteoclasts and MGCs in bone homeostasis and foreign body reactions, respectively. Thus, the role of the cell–cell fusion of osteoclasts in bone homeostasis has been, at least in part, clarified. Furthermore, macrophages reportedly fuse not only with macrophages in a homophilic manner but also with somatic cells and tumors in a heterophilic manner, and the heterophilic fusion is considered involved in tissue repairs and tumor metastasis. Similar to this heterophilic cell–cell fusion, some types of virus such as human immune deficiency virus and influenza virus fuse to somatic cells during an infection. In this chapter, recent advances in the molecular understanding of cell–cell fusion in macrophages will be discussed. [ABSTRACT FROM AUTHOR]

Successful mammalian fertilization results in the union of two gametes, a spermatozoon and a mature oocyte. Membrane fusion events are essential for at least two distinct steps of the fertilization process: (i) the vesiculation of the acrosomal surface membranes during sperm acrosomal exocytosis (AE), induced by sperm binding to the egg-coat, and (ii) fusion of the oocyte plasma membrane, the oolemma, with the sperm plasma membrane that occurs after AE and sperm-egg coat penetration. The rearrangement of sperm plasma membrane domains/membrane lipid raft formation during sperm capacitation in the female reproductive tract is a priming step that enables the fusion and vesiculation of outer acrosomal membranes during AE. The membrane fusion/vesiculation events of AE seem to share similarities with synaptic vesicle fusion, assisted by the membrane proteins of the SNARE hypothesis. The AE exposes the transmembrane receptors on the sperm head equatorial segment in preparation for sperm-oolemma adhesion and fusion. Gene ablation studies indicate that the tetraspanin family proteins CD9 and CD81 on the oolemma interact with the superglobulin family protein IZUMO on the sperm plasmalemma to mediate sperm-oolemma adhesion in mammals. The fusogenicity of IZUMO has not been established, so the involvement of this system in the actual membrane fusion part of sperm–oolemma interaction remains open. Interactions of ADAM family proteins on sperm plasma membrane with oolemma integrins appear non-essential during sperm-oolemma fusion, but integrins may play a supporting role via sustenance of the tetraspanin web in the oocyte cortex. Sperm-oolemma binding may be reinforced by a cast of other receptors found on the surface of the sperm head (e.g. CRISP and MN9). The present chapter reviews recent progress in the study of these fundamental factors of gamete membrane fusion during mammalian fertilization. [ABSTRACT FROM AUTHOR]

In fertilization, two types of sex cells or gametes – a sperm and an egg – unite in a stepwise manner to form a mother cell, which is capable of developing naturally into a new individual. Notably, the ˵membrane fusion″ that occurs intercellularly between a sperm and an egg is essential for fertilization. A sperm factor that is delivered into the egg cytoplasm through fusion serves to activate a signaling pathway; this leads to the resumption of meiosis in the egg. In mammals, sperm-egg fusion is partly mediated by two integral membrane proteins, sperm Izumo (Inoue et al. 2005) and egg cluster of differentiation 9 (CD9) (Kaji et al. 2000, Le Naour et al. 2000, Miyado et al. 2000), and the roles played by both are critical but yet unknown. A recent study (Miyado et al. 2000) showed that CD9-containing vesicles are released from wild-type eggs, and that these exosome-like vesicles induce fusion between sperm and CD9-null eggs in vitro, even though CD9-null eggs are highly refractory to sperm-egg fusion. This result provides compelling evidence for the crucial involvement of CD9-containing, fusion-facilitating vesicles in sperm-egg fusion and offers new insight into both gamete fusion and other membrane fusion events. [ABSTRACT FROM AUTHOR]