Macrophages

Introduction

Macrophages are a vital component of the human immune system, responsible for phagocytosis of pathogens, removal of debris and dead cells, and activation of other immune cells. Macrophages provide innate immunity, serving as the initial defense against foreign antigens. Adaptive immunity is a specific part of the immune system that includes specialized immune cells and antibodies. Macrophages not only play a part in the immune system but also release anti-inflammatory cytokines and assist in repairing processes.

What Are Macrophages?

Macrophages originate from monocytes, which are derived from the bone marrow. Monocytes travel in the bloodstream for one to three days before moving into tissues, where they transform into macrophages or dendritic cells, a type of antigen-presenting cell involved in connecting innate and adaptive immunity. Macrophages are present in several organs, such as the liver, brain, bones, and lungs, as well as in the blood, especially in areas of infection.

What Are the Classifications of Macrophages?

Macrophages can be broadly classified into two primary types: M1 and M2 macrophages.

• M1 macrophages, known as classically-activated macrophages, are activated by pathogen invasion and are crucial in the immune response to foreign pathogens like bacteria.

• M2 macrophages, also known as alternatively-activated macrophages, are involved in wound healing tissue repair and have anti-inflammatory functions.

What Is the Role of Macrophages?

Macrophages eliminate pathogens, remove dead cells, and promote tissue repair in the body. They also have a significant part in the formation of granulomas, which are clusters of macrophages that work to contain an infection.

M1 Macrophages

• M1 macrophages specialize in identifying, engulfing, and eliminating germs. They can accomplish this by phagocytosis, a process where a connection is established between cellular receptors on the macrophage and surface antigens on the bacteria. After the bridge is established, the macrophage's membrane extends outward and encircles the bacteria. Upon entering the macrophage, the bacteria becomes enclosed in a phagosome, a vesicle that merges with a lysosome. The lysosome has enzymes and peroxides capable of breaking down the pathogen.

• M1 macrophages facilitate inflammation, extracellular matrix (ECM) degradation, death of invading cells by releasing cytokines and nitric oxide, and antigen presentation, functioning as antigen-presenting cells (APCs).

• Once a macrophage has processed and digested the antigen, a major histocompatibility complex (MHC) molecule presents the antigen on the macrophage's surface for binding with a T-cell receptor. This initiates the adaptive immune system in the body to identify the foreign antigen and activate additional processes to eliminate the cells.

M2 Macrophages

• M2 macrophages are essential for the regeneration of connective tissue in wound healing. They secrete vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β1 to promote vascular stability and facilitate wound healing.

• M2 macrophages also work to engulf pathogens and damaged tissue near the wound. They can remove damaged tissue by releasing digestive enzymes that break down proteins.

• They release growth factors to induce cell re-epithelialization of the wound, generate granulation tissue, and form a new extracellular matrix.

Other Functions

• Macrophages have extra functions in certain organ systems, as the air is breathed in for oxygen exchange; harmful things, including bacteria, viruses, and fungi, can enter the lungs, particularly the alveoli (air sacs in the lungs).

• Alveolar macrophages in the lungs may eliminate bacteria and harmful substances, preventing diseases like tuberculosis by forming granulomas.

• Kupffer cells are a type of macrophage found in the liver; they remove possible infections from the liver that may have entered the bloodstream from the gastrointestinal system. They regulate iron levels and play a role in the metabolism of bilirubin. When the liver is damaged, Kupffer cells release anti-inflammatory cytokines such as Interleukin.

• Microglia are the brain's macrophages that exhibit a neuroprotective influence by releasing several anti-inflammatory cytokines and nerve damage factors. When neurons are destroyed, microglia are called to the location to engulf dead cells and foreign substances to avoid additional tissue damage.

Are Macrophages Beneficial or Harmful?

Macrophages are beneficial and have a crucial function in the human body. They defend the body against bacterial and viral infections by releasing antimicrobial substances and pro-inflammatory cytokines and promoting healing through an anti-inflammatory reaction. They protect against neuronal damage in the brain and regulate iron and bilirubin levels in the liver.

• There are certain pathogenic outcomes associated with macrophages. One form of M2 macrophage, tumor-associated macrophage (TAM), facilitates tumor growth by inhibiting the immune system; treatments are being created to address TAMs specifically.

• M1 and M2 macrophage populations contribute to the development of atherosclerosis, an arterial disease marked by fat accumulation on the walls of blood vessels. M1 macrophages induce vascular inflammation, while M2 macrophages eliminate cholesterol from blood arteries, leading to their oxidation and the formation of atheromatous plaques. Hypertension and cardiovascular disease may result from this mechanism.

What Function Do Macrophages Serve in Pathological Processes?

Macrophages are recognized as significantly impacting various diseases linked to chronic inflammation, such as atherosclerosis, obesity, diabetes, cancer, skin conditions, and neurological disorders. It is, therefore, not surprising that macrophages in human diseases have attracted great interest in recent years, such as below.

• Macrophage activation syndrome results from extensive macrophage activation, commonly observed in conditions such as systemic problems associated with SARS-CoV-2, including acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation syndrome, edema, and pneumonia.

• Atherosclerosis is a persistent condition that begins when monocytes enter the subendothelium and transform into macrophages. Macrophages are the primary immune cells in atherosclerotic plaques and play a crucial role in the development and evolution of these plaques. Research has shown that resident macrophages can multiply in response to specific environmental conditions and play a significant role in the buildup of macrophages in plaques during all phases of atherosclerosis.

• Hepatic macrophage populations consist of several cells with adaptable characteristics that can transform into distinct phenotypes to adjust their features in reaction to various stimuli. They frequently control the function of other cells and are crucial in several liver disorders. When faced with abnormal conditions, these cells become active and release cytokines and chemokines, which can draw monocytes from the bloodstream and perform actions that worsen the symptoms.

• Adenoviruses, HIV, and the bacteria responsible for tuberculosis are germs that cause illness by invading macrophages.

• Macrophages in adipose tissue can trigger inflammation, leading to insulin resistance in adipocytes. This may result in the onset of diabetes.

• Macrophages can produce chronic inflammation, which in turn can promote the formation and proliferation of cancer cells.

Conclusion

Macrophages are a type of white blood cell essential in the immune system since they engulf foreign antigens, including bacteria, through phagocytosis. They can display these antigens to other immune cells, such as T-cells, for additional elimination. Macrophages are involved in wound healing and tissue restoration. They draw anti-inflammatory cytokines to the wound site, which promote vascular development and possess microcidal capabilities. Macrophages are crucial in maintaining tissue balance in humans but can also be involved in developing diseases. This occurs when tumor-associated macrophages resist immune system inhibition and stimulate tumor growth or when macrophages contribute to the development of atherosclerosis in arteries.