Chronic inflammation can cause serious health issues, including dreaded conditions such as cancer. Researchers from Japan have now made a discovery that could help to better fight it.
Neutrophils Interacting With Macrophages
Inflammation is not a bad thing until it turns chronic. It occurs when the body senses the presence of something that is not normal, such as infections or injuries. The immune system sends out cells to attack possible invaders. But when inflammation turns chronic – persists after an injury or infection resolves – it turns problematic.
The researchers in this new study found that neutrophils trigger inflammation-fighting macrophages deep inside granulocytes, which are white blood cells with small enzyme granules. Explicitly, they induce M2 macrophages.
Polarization of macrophages
Macrophages are dedicated cells that play a critical role in the detection and destruction of harmful organisms in the body. They are a type of white blood cells that move around looking for potential pathogens to engulf on detection and destroy.
Macrophages are basic cellular factors in chronic inflammatory responses. Researchers reported in previous studies that chronic inflammatory macrophages possess the ability to polarize into two distinct populations: M1 and M2.
M1 macrophages are pro-inflammatory while the M2 variants are anti-inflammatory. A fine balance of these two populations is critical for the effective regulation of inflammation and tissue health.
Researchers say this macrophage polarization explains how M2 can be restored to M1 in deep inflammation areas or granuloma zones where there is a “bacteria-permissive microenvironment.”
“Microbes and cancer cells may manipulate this permissive microenvironment to favor their survival,” explained Tatsuaki Mizutani, who is the first author of the paper.
The polarization also accounts for a reversion to M0, which refers to the non-inflammatory state.
Neutrophils and granuloma-related disorders
A release of granulocytes marks the beginning of a variety of immune responses when the body senses an infection. Neutrophils are a major type of granulocytes that help the body to fight off bacterial and fungal infections.
According to researchers, neutrophils often exhibit zero tolerance for risky bacteria and fungi. But a balanced, less brutal approach can help even more when it comes to having a cure.
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Tuberculosis and other granuloma-related conditions are typical of chronic inflammatory diseases in humans. Previous research has shown that intracellular interactions in granulomas fuel strong inflammatory responses against harmful agents and toxins in the body.
However, chronic inflammation seen in conditions such as tuberculosis and cancers carries on for extended periods.
Previously, Mizutani and his colleagues established a lung granuloma model in guinea pigs intending to predict tumor development. They observed a buildup of Neutrophil S100A9 (also called A9) deep in granuloma cores.
A9 is expressed at low levels in both monocytes and macrophages. However, researchers say there is a high expression within neutrophils.
“What is interesting is that both the inflammatory and anti-inflammatory effects of A9 have been reported in A9-deficient mice,” Mizutani observed.
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The researchers believed that the results they got from tuberculosis may be applied to tumors as well. They are now thinking of exploring the multifunctional nature of A9 for anti-tumorigenic purposes in the tumor microenvironment.
The team is hopeful that a better grasp of a permissive tumor microenvironment may be useful for making potent cancer drugs.
References
Neutrophil S100A9 supports M2 macrophage niche formation in granulomas
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