Monocyte and Multinucleated Cells

Dear Colleagues,

Monocytes are the largest of the leukocytes. They exist in all vertebrates and are produced in the bone marrow before being released into circulation. Monocytes travel from the circulation into the tissues and differentiate into macrophages and monocyte-derived dendritic cells. Monocytes are vital in the defense against pathogens and are implicated in autoimmune and inflammatory diseases. Blood monocytes have three subtypes: classical, intermediate, and non-classical. The subtypes vary in their cytokine secretion and cell surface markers.

Monocytes can fuse to form multinucleated giant cells (MGCs), such as the bone-resorbing cells osteoclasts. Osteoclast MGCs are about ~100 μm in diameter with up to 20 nuclei. Monocytes also fuse to form inflammatory MGCs, such as Langhans giant cells (LGCs) in response to M. tuberculosis infection. LGCs sequester the pathogen within the host. MGCs have been observed in breast cancer, lung cancer, gastric cancer, lymphoma, and esophageal cancer. By phagocytosing cancer cells, MGCs prevent lymph node metastasis. In response to foreign materials, such as medical implants, monocytes can fuse to form foreign body giant cells (FBGCs), which produce and release ROS in an attempt to degrade and digest a foreign material.

The formation of giant cells through monocyte fusion is still not thoroughly understood, and only a few important proteins playing a role in this process have been described. LGC and FBGC formation is initiated by different cytokines, such as IFNγ and IL-4. The monocyte fusion is activated by fusogenic stimuli, such as CCL2 and CCL3, which upregulate cell–cell adhesion proteins, such as LFA-1, ICAM-1, and E-cadherin, and upregulate fusion-facilitating proteins, such as CD200, SIRPα/CD172a/MFR, CD47, CD36, CD62E (E-selectin), matrix metallopeptidase 9 (MMP9), and dendrocyte-expressed seven transmembrane protein (DC-STAMP).

Although monocytes per se are not present in invertebrates, some invertebrates, such as clam Mercenaria mercenaria, can form multinucleated giant cells morphologically similar to Langhans cells and foreign body giant cells and they phagocytose parasites and sequester environmental pollutants. Another example is Drosophila, which has multinucleated giant hemocytes (MGHs) in the blood equivalent, hemolymph. MGHs are gigantic cells with multiple nuclei. They are highly motile and functionally similar to mammalian inflammatory MGCs by sequestering and killing pathogens/parasites.

The presence of multinuclear giant cells not only in vertebrates but also in invertebrates indicates that their formation and functions are evolutionarily ancient.

Prof. Dr. Malgorzata Kloc
Dr. Ahmed Uosef
Guest Editors

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