A new study has clarified how giant cells made of fused immune cells dispose of bulky waste material that might otherwise clog up the body’s biology. The findings help to resolve some unanswered questions surrounding so-called multinucleated giant cells. They might also explain why a new treatment for systemic amyloidosis – a rare but serious condition caused by deposits of abnormal protein – may be showing success in trials.

giant cells and macrophagesShare on Pinterest
Two giant fused cells – one in the center adherent to its target, the other lower left semi-adherent – surrounded by phagocytic cells. The blue spots are nuclei.
Image credit: Ronny Milde / TUM

The study, which is published in the journal Cell Reports, is the work of researchers from the Technical University of Munich (TUM) in Germany and University College London (UCL) in the UK.

Multinucleated giant cells (MGCs) were first discovered over 100 years ago. They occur in certain chronic inflammatory diseases such as tuberculosis (TB) and also in response to foreign material invading tissue – they appear, for instance, in reaction to implants such as artificial hips.

MGCs are known to arise from the fusion of phagocytes – immune cells that protect the body by devouring bacteria, harmful foreign particles and dead or dying cells.

However, many of the mechanisms underlying the activity of these giant cells have not been well understood, as co-senior author Dr. Admar Verschoor, who leads a group in TUM’s Institute for Medical Microbiology, Immunology and Hygiene, explains:

Because they are so big and derive from multiple phagocytic cells, it had been suggested that they may act as specialized 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 study has two strands – one involves a series of elaborate cell experiments and the other investigates what happens in systemic amyloidosis.

Systemic amyloidosis is a group of rare diseases caused by the build-up of unstable proteins outside cells, such as in the blood. The protein deposits damage organs such as the heart, liver, spleen, kidney and gut. The result is organ malfunction and, eventually, death. Current treatment options for these diseases are limited.

Prior to the study, co-senior author Mark B. Pepys, a professor of medicine who runs the Centre for Amyloidosis and Acute Phase Proteins at UCL, had already successfully tested a new treatment for systemic amyloidosis, which – among other things – promotes the formation of giant cells.

But Prof. Pepys says they could not fully explain why the treatment worked. That is why the UCL team linked up with the TUM team’s expertise in phagocytic cells and the immune system.

When they brought together what they observed in the cell culture experiments with the amyloidosis disease model, the researchers could see a mechanistic explanation for how and why the giant cells target and devour the abnormal amyloid protein deposits.

One of the things they observed is when the phagocytes fuse together to make a giant cell, the big cell has a ruffled, excess membrane that provides for ingestion of large materials.

However, it appears that not only does the treatment promote the formation of the giant cells; it also coats the abnormal protein deposits with molecules that serve as what the researchers refer to as “complement.” The giant cells “relish” and devour the complement-coated material, as Dr. Verschoor explains:

Complement acts a bit like the butter on our bread. Just like bread tastes better with a bit of butter on it, the pathogenic protein deposits in amyloidosis become more attractive for giant cells with a bit of complement on them.”

The researchers were able to observe the devouring process under the microscope. They could see the large phagocytic cells surrounding and destroying the disruptive protein clumps.

“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,” concludes Dr. Verschoor.

Meanwhile, from other recently published research, Medical News Today learned of a method to eliminate cancer in lymph nodes using laboratory-enhanced natural killer cells. The team working on the approach has successfully tested the method in mice, and should it work in humans, it could stop cancer spreading to the rest of the body via lymph nodes.