What Are Tumor-Associated Macrophages?

Macrophages (English: Macrophages, abbreviated as mø ) are white blood cells located in tissues, derived from monocytes, and monocytes are derived from precursor cells in the bone marrow. Both macrophages and monocytes are phagocytes, and participate in non-specific defense (innate immunity) and specific defense (cellular immunity) in vertebrates. Their main function is to phage (ie, phagocytose and digest) cell debris and pathogens in the form of fixed cells or free cells, and activate lymphocytes or other immune cells to make them respond to pathogens. Macrophages belong to immune cells and have a variety of functions. They are important objects for studying cell phagocytosis, cellular immunity, and molecular immunology. Macrophages are easy to obtain, easy to culture, and can be purified. Macrophages are non-reproductive cell populations and can live for 2 to 3 weeks under suitable conditions. They are mostly used for primary culture and difficult to survive for a long time.

Macrophage cells, also known as histocytes, are formed by monocytes in the blood that penetrate the blood vessels and differentiate. After monocytes enter connective tissue, their volume increases, endoplasmic reticulum and mitochondria proliferate, lysosomes increase, and phagocytosis is enhanced. The life span of macrophages varies depending on the tissues and organs in which they live, and they can generally survive for months or longer.

The differentiation of monocytes into macrophages is accompanied by certain phenotypic changes, including:

Cell surface receptors such as complement iC3b and transferrin receptor expression increase;

Intracellular enzymes such as -amino glycoside esterase, creatine kinase, tissue transglutaminase, and cAM-dependent protein kinase have increased expression;

The ability to secrete hydrogen peroxide and superoxide ions is reduced. At the same time, this process is also significantly negatively regulated by IFN- and hormones ^[1]

Macrophages are widely distributed, with large numbers in loose connective tissue. Macrophages have a variety of morphologies, which change due to different functional states. They are generally round or oval with short protrusions. Active people often extend longer pseudopods and are irregular. Nuclei are small, round or oval, and darker in color. Under the scanning electron microscope, there were many micro-folds and protrusions on the cell surface, which were colored balls. Under transmission electron microscopy, the cytoplasm contains a large number of primary lysosomes, secondary lysosomes, phagosomes and phagosomes, in addition to the more developed Golgi complex, a small amount of mitochondria, and rough endoplasmic reticulum. Macrophages can be adhered to glass and plastic surfaces during in vitro culture, and their cytoplasmic non-specific lipase is positive, which is often used to collect and identify macrophages ^[1]

Excluding granules and lymphocytes, about 5% of the remainder are macrophages. Macrophages are amoeba-like cells that swallow and process large foreign bodies, old waste excreted by cells, red blood cells at the end of life, etc. They also go to the site where inflammation occurs to process foreign bodies. They are a white blood cell with a wide range of guardianship.

Macrophages are not only present in the blood, they are also distributed throughout the body. Names and shapes vary depending on where they are located. Monocytes circulate throughout the body with the blood, running towards the site of inflammation. Lung macrophages are active in the lungs, liver macrophages are active in the liver, and glial cells are active in the brain.

The defense system in the era of single-celled organisms is quite simple. Macrophages engulf foreign bodies and make them excrete into the body. However, when the body is constantly threatened by viruses and foreign proteins (proteins that it should not have), it cannot survive by relying on such a degree of defense system. As the organism evolved towards vertebrates, a new defense system was formed.

A tiny foreign body like a virus is more effective than an engulfing attack. Therefore, the lymphocytes that gave up the phagocytosis ability of macrophages and mainly produced the function of entanglement of the enemy with antibodies appeared; and the granule spheres that further enhanced the phagocytosis ability of macrophages ^[2]

When monocytes enter a damaged tissue through the endothelial cell layer of a blood vessel (a process called leukocyte extravasation), it undergoes a series of transformations to become macrophages. Monocytes are attracted to damage by chemical stimuli due to chemical tropism. These stimuli include injured cells,

Macrophages also have infinite

Peritoneal separation

1. Take about 6 weeks of mice (or about 600 grams

Macrophage migration inhibitory factor (MIF)

In the process of body wound repair, macrophages have two main functions.

First, once the body's traumatic activities begin, macrophages can secrete a large variety of

After the macrophages rupture, this pigment is also visible extracellularly. Hemoflavin was stained blue by Prussian blue due to Fe3 +. LaihoK reports that in the human body, iron phagocytic cells appear in the skin and subcutaneously 21 to 48 hours after injury bleeding, and more in 4 to 8 days. BetzP et al. Studied human skin injury specimens and found that hemosiderin was detected as early as 3 days after injury and 8 days after injury.

Macrophages can engulf and damage damaged tissue and help initiate the healing process. Although they play a key role at the site of the injury, once the task is completed, they need to be evacuated as soon as possible to end the inflammatory response and open the way for the regeneration process. Persistent macrophages are not conducive to tissue recovery.

As a kind of plastic and pluripotent cell population, macrophages show obvious functional differences under the influence of different microenvironments in vitro and in vivo. According to different activation states and functions, macrophages can be mainly classified into M1 type, which is classically activated macrophages, and M2 type, which is alternately activated macrophages.

Macrophages are a very heterogeneous cell population that exhibit unique phenotypes and functions in the complex microenvironment of the body. Mantovani et al. Believe that macrophages have a series of continuous functional states, and M1 and M2 macrophages are the two extremes of this continuous state. M1 macrophages secrete pro-inflammatory cytokines and chemokines, and present antigens on a full-time basis, and participate in the positive immune response to play the role of immune surveillance; M2 macrophages have only weak antigen presentation capabilities, and By secreting inhibitory cytokines such as IL-10 or TGF-B, it can down-regulate the immune response and play an important role in immune regulation. Identifying the type of macrophages by phenotype is of great significance in studying the functions of macrophages under different physiological and pathological conditions. However, there are no recognized phenotypic markers to identify and distinguish different types of macrophages, and the phenotypic characteristics of M1 and M2 macrophages are inconclusive.