Creative Biolabs summarizes the current knowledge on the phenotype, function, disease relevance, and therapeutic application of Mox macrophages.

Phenotype of Mox Macrophages

Mox macrophages are characterized by their distinctive macrophage morphology and molecular profile, which distinguish them from other types of polarized macrophages.

• Morphologically, Mox macrophages are foamy and multinucleated, which reflect their high capacity of phagocytosis and proliferation. They also have a large cytoplasm and a prominent Golgi apparatus, which indicate their active secretion and metabolism.
• Molecularly, Mox macrophages express a set of specific markers that can be used to identify them. These include surface receptors, such as CD36, CD68, CD163, CD206, CD11b, and CD11c, which are involved in the recognition and uptake of oxPLs and other ligands. They also include transcription factors, such as peroxisome proliferator-activated receptor gamma (PPARγ), nuclear factor erythroid 2-related factor 2 (NRF2), and heme oxygenase-1 (HO-1), which are responsible for the regulation of Mox-specific genes.
• Moreover, Mox macrophages display a unique gene expression profile that reflects their functional state. For example, they upregulate genes related to lipid metabolism (such as ABCA1, ABCG1, LXRα, and SREBP1), antioxidant defense (such as NQO1, GCLC, GCLM, and GPX1), and anti-inflammatory cytokines (such as IL-10 and TGF-β).

Mox macrophages are not a homogeneous population, but rather a heterogeneous group of cells that can be further classified into different subtypes based on their origin, location, stimulus, and function.

• Mox macrophages can be derived from monocytes or resident macrophages in tissues, such as the liver, lung, adipose tissue, or atherosclerotic plaques.
• They can also be induced by different types of oxPLs or other oxidative stressors, such as oxidized LDL (oxLDL), oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), 4-hydroxynonenal (4-HNE), or hydrogen peroxide (H₂O₂).
• Furthermore, Mox macrophages can exhibit different functions depending on the context and environment they are in. For example, they can have pro-inflammatory or anti-inflammatory effects on the surrounding cells and tissues.

Functions of Mox Macrophages

Mox macrophages have various functions that are related to their phenotype and molecular profile.

• Macrophage Phagocytosis
  • Mox macrophages can recognize and clear oxPLs and other oxidative substances by using their surface receptors, such as CD36, which is a scavenger receptor that binds to oxLDL and other ligands.
  • By doing so, Mox macrophages can prevent the accumulation of oxPLs and protect the cells and tissues from oxidative damage.
• Secretion
  • Mox macrophages can secrete a variety of factors that have different effects on inflammation and metabolism, produce anti-inflammatory cytokines, such as IL-10 and TGF-β, which can inhibit other immune cells and suppress the inflammatory response, produce chemokines, such as CCL2 and CCL5, which can attract other immune cells to the site of inflammation or injury, and produce antioxidant factors, such as HO-1 and NQO1, which can scavenge ROS and protect the cells and tissues from oxidative stress.
• Regulation
  • Mox macrophages can regulate lipid metabolism and inflammation by using their transcription factors, such as PPARγ, which is a nuclear receptor that controls the expression of genes involved in lipid homeostasis and inflammatory signaling.

Therefore, Mox macrophages have multiple functions that are influenced by their phenotype and molecular profile. Depending on the context and environment they are in, Mox macrophages can have beneficial or detrimental effects on oxidative stress and inflammation.

Role of Mox Macrophages in Diseases

Mox macrophages are involved in various diseases that are associated with oxidative stress and inflammation.

• Mox macrophages are abundant in atherosclerotic plaques, especially in the necrotic core, where they are exposed to high levels of oxPLs and oxLDL.
• Mox macrophages are present in obese adipose tissue, where they are induced by oxPLs and other oxidative stressors that are generated by adipocytes or infiltrated immune cells.
• Mox macrophages are found in diabetic organs and tissues, where they are induced by oxPLs and other oxidative stressors that are produced by hyperglycemia or dyslipidemia.

Besides atherosclerosis, obesity, and diabetes, Mox macrophages are also implicated in other diseases that involve oxidative stress and inflammation, such as liver cirrhosis, pulmonary fibrosis, neurodegenerative diseases, etc. In these diseases, Mox macrophages may have similar or different roles as in the above-mentioned diseases, depending on the specific pathophysiology and microenvironment of each disease. Therefore, Mox macrophages are a versatile and dynamic type of polarized macrophages that have diverse and complex effects on various diseases.

Therapeutic Application of Mox Macrophages

Mox macrophages have a potential therapeutic value for the treatment of diseases that are associated with oxidative stress and inflammation. One of the possible ways to use Mox macrophages for therapy is to modulate their phenotype and function by using pharmacological agents or genetic manipulations.

• For example, by activating or inhibiting their transcription factors, such as PPARγ, NRF2, or HO-1, one can enhance or suppress their anti-inflammatory and antioxidant functions, respectively.
• Another example is to manipulate their surface receptors, such as CD36, which are responsible for the uptake of oxPLs and other ligands. By blocking or enhancing their expression or activity, one can decrease or increase their phagocytic and foam cell formation functions, respectively.

Another possible way to use Mox macrophages for therapy is to transplant them into the diseased organs and tissues, where they can exert their beneficial effects by performing their functions.

Therefore, Mox macrophages have a potential therapeutic value for the treatment of diseases that are associated with oxidative stress and inflammation.

References

1. Serbulea V, et al. "Macrophage phenotype and bioenergetics are controlled by oxidized phospholipids identified in lean and obese adipose tissue". Proc Natl Acad Sci U S A, (2018).
2. Gill N, et al. "The immunophenotype of decidual macrophages in acute atherosis". Am J Reprod Immunol, (2019).
3. Wang L, et al. "Ironing out macrophages in atherosclerosis". Acta Biochim Biophys Sin (Shanghai), (2023).