Reprogrammed macrophage would act as anti-inflammatory and aids in tissue repair

Macrophages are a type of white blood cell that serves as the first line of defense against any invading pathogen in almost every part of the body. It engulfs and digests cellular debris, foreign pathogens, cancer cells by the process called phagocytosis. Besides eating the cell, it also plays an important role in innate and adaptive immunity. It helps to present antigen to the T cells with the help of an MHC molecule. Also, depending on the signal they get, it can either increase inflammation or decrease it and causes the affected area to heal.

Those macrophages which encourage inflammation are called M1 cells, and those which decrease inflammation are called M2 cells. These are mainly regulated by the signal that causes the programming of genes in macrophages. This mechanism senses the body to prevent further inflammation and promote tissue repair after it has encountered the inflammatory immune cells. When this process gets hampered, it will pave the way for autoimmune disorder and also Acute Respiratory Distress Syndrome (ARDS), which is a common sequel in some COVID-19 patients.

More about M1 and M2

The pro-inflammatory macrophages (M1) are induced by microbial products, such as the Lipopolysaccharides (LPS) and other Toll-like receptor ligands, or by the cytokines secreted by T-helper 1 cells, such as Interferon-gamma and TNF. These all signals favor the expression of specific genes, causing transcription, and end up in inflammation.

M2 or anti-inflammatory macrophages are induced by IL-4 or IL-13 secreted by innate and adaptive immune cells, such as mast cells, basophils, and T-helper 2 cells. These all favors anti-inflammatory profile and permit resolution of inflammation and tissue repair and wound healing. Some even stimulate angiogenesis by producing vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF).

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The study

Researchers at the University of Illinois Chicago conducted a study on animal lung injury models focusing on macrophage programming. They found the programming process was even more complex than they previously had thought. The study has hinted that macrophage programming is not controlled by the immune system alone, rather it is also influenced by the microenvironment in which the macrophage resides.

Lung endothelial cells are the one which programs the macrophages to function as an anti-inflammatory and also promotes healing. Researchers try to analyze the protein secreted by the endothelial cells, which triggers the macrophages to knock out M1 property that will promote inflammation and add more damage. They identified one protein called Rspondin3, that elevated during inflammation, and stimulate M2 properties. When the gene producing Rspondin3 removed from the blood vessels, the macrophage was not able to decrease inflammation, and the lung became more injured. They have done the same experiment on different animal models and showed consistent results, which then proved that the endothelial cells could help the macrophages to program themselves.

This study showed that why some people suffer severe lung injury or ARDS, especially in the case of the current COVID-19 pandemic, although many people recover from a lung infection. It might be because of people who have poor vascular health, and so the blood vessels fail to produce appropriate signals to the macrophages to subside the inflammation. The inability of a person to turn off the inflammation once after a virus or bacteria has eliminated would result in severe damage to the tissues or organs. Though this study depicts only the lung, it can also describe diseases in other organs like the brain, liver, heart, probably due to the dysregulation of the immune cells.

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Source: Medical Xpress

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