How Giant Cells Dispose of Giant Waste

PHAGOCYTIC multinucleated giant cells (MGCs) act as the waste disposal men of the body by clearing away bulky waste materials that carry the potential to clog bodily systems, according to the results of a recent study. These data contribute to our understanding of MGCs, and may also explain why a novel treatment for systemic amyloidosis has shown success in recent clinical trials.

MGCs occur in particular chronic inflammatory diseases, such as tuberculosis, and in response to tissue-invading foreign material. It has been established that the giant cells arise from the fusion of phagocytes, however the mechanisms by which MGCs operate remain ambiguous, as Dr Admar Verschoor, Institute for Medical Microbiology, Technical University of Munich (TUM), Munich, Germany, explained: “Because they are so big and derive from multiple phagocytic cells, it had been suggested that they may act as specialised disposal units for particular forms of waste. But a definitive confirmation or a molecular and cellular basis for this theory was so far lacking.”

The new study, conducted by a TUM research group, involved a series of cellular experiments and an investigation into systemic amyloidosis, a group of rare diseases with limited treatment options triggered by a build-up of unstable proteins outside cells, such as in the blood. These deposits cause organ malfunction and eventually death. A research team from the Centre for Amyloidosis and Acute Phase Proteins, University College London, London, UK, who recently tested a new treatment for systemic amyloidosis that promotes MGC formation, joined forces with the TUM team to elucidate the mechanisms behind the success of their treatment.

Combining observations from cellular experiments with the amyloidosis disease model allowed researchers to achieve an explanation for how and why MGCs target and devour amyloid protein deposits. Researchers observed the giant cells under the microscope, and noted the MGCs surrounding and destroying disruptive protein clumps. They also saw that when phagocytes fused to produce MGCs, the giant cells presented ruffled, excess membranes that accommodate the ingestion of large materials. In addition to promoting MGC formation, the amyloidosis treatment also appeared to facilitate the coating of protein deposits with a layer of molecules dubbed a ‘complement’; MGCs ‘relish’ and devour complement-coated material, suggesting that the complement makes the pathogenic deposits more attractive to MGCs.

Dr Verschoor concluded: “Our studies show that giant cells are particularly well suited to remove large targets that are complement-marked, explaining why they can act so effectively in the promising new treatment for systemic amyloidosis.”

(Image: freeimages.com)

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