The Properties And Functions Of Macrophages

Macrophages are specialized cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms.

In addition, they can also present antigens to T cells and initiate inflammation by releasing molecules (known as cytokines) that activate other cells. Macrophages originate from blood monocytes that leave the circulation to differentiate in different tissues.

There is a substantial heterogeneity among each macrophage population, which most probably reflects the required level of specialization within the environment of any given tissue.

Macrophages migrate to and circulate within almost every tissue, patrolling for pathogens or eliminating dead cells. 

In this article we will answer any and all questions regarding the difference between macrophages, monocytes and neutrophils, as well as how macrophages are located, how they function and more!

So, if you’ve got some burning questions on macrophages, read on for the answers!

Where Can Macrophages Be Found?

Macrophages that reside in adult healthy tissues either derive from circulating monocytes or are established before birth and then maintained during adult life independently of monocytes.

By contrast, most of the macrophages that accumulate at diseased sites typically derive from circulating monocytes.

When a monocyte enters damaged tissue through the endothelium of a blood vessel, a process known as leukocyte extravasation, it undergoes a series of changes to become a macrophage.

Monocytes are attracted to a damaged site by chemical substances through chemotaxis, triggered by a range of stimuli including damaged cells, pathogens and cytokines released by macrophages already at the site.

At some sites such as the testis, macrophages have been shown to populate the organ through proliferation.Unlike short-lived neutrophils, macrophages survive longer in the body, up to several months.

Macrophages are essential for the maintenance and defense of host tissues, doing so by sensing and engulfing particulate matter and, when necessary, initiating a pro-inflammatory response.

They migrate to and circulate within almost every tissue, patrolling for pathogens or eliminating dead cells.

Playing such a vast number of roles in both health and disease, the activation phenotype of macrophages can vary greatly ( substantial heterogeneity) and is largely dependent on the surrounding microenvironment – reflecting the required level of specialization within the environment of any given tissue.

This heterogeneity is reflected in their morphology, the type of pathogens they can recognise, as well as the levels of inflammatory cytokines they produce.

Macrophages also produce reactive oxygen species, such as nitric oxide, that can kill phagocytosed bacteria.

How Are Macrophages Formed?

Macrophages are formed through the differentiation of monocytes, one of the major groups of white blood cells of the immune system.

When there is tissue damage or infection, the monocytes leave the bloodstream and enter the affected tissue or organ and undergo a series of changes to become macrophages.

These macrophages can modify themselves to form different structures in order to fight various different microbes and invaders. In this way, macrophages provide the first line of defense in protecting the host from infection.

The macrophages present in humans are around 21 micrometers in diameter. They can survive for months at a time. They are also involved in the development of non-specific or innate immunity.

This type of immunity is a long-term immunity which is acquired when a macrophage ingests a microbe and presents the microbe’s antigen on its surface to alert other white blood cells to the presence of the invading particle.

Other white blood cells then multiply and amount an immune response against the pathogen.

In addition, the pathogen displaying the antigen can be recognized and targeted directly by antibodies should future reinfection occur, meaning that the pathogen is in a sense “remembered” by the immune system.

Some examples of macrophage cells and where they can be found in the body are;

• Alveolar macrophage: These macrophages are found in the Lung alveoli, hence the name. The principal function of these cells is the phagocytosis of dead cells or bacteria. Additionally, they also initiate and control immunity to a wide array of respiratory pathogens.

• Kupffer cells: Kupffer cells are found in the liver, within the lumen of the liver sinusoids. These bring about immune responses and tissue remodeling.

• Microglia: These cells belong to the central nervous system and are responsible for the elimination of old or dead neurons. Additionally, they also control the immunity in the brain.

• Splenic macrophages: These cells are found in the Spleen and help in the elimination of dysfunctional or old red blood cells, from the body.

The Function Of A Macrophage

In the next part of the article, we will discuss the location and function of a few different macrophage populations.

• Alveolar macrophage: Lung alveoli – Phagocytosis of small particles, dead cells or bacteria. Initiation and control of immunity to respiratory pathogens. The first line of defense against invading respiratory pathogens. They reside in pulmonary alveoli and the interalveolar septum in close proximity with pneumocytes.

• Histiocytes: Connective Tissue – Motile, phagocytic cells found in the loose connective tissue throughout the body, help the body heal after an injury or infection by removing dead cells, blood, micro-organisms (such as bacteria and fungus), and foreign material from the body.

• Osteoclasts: Bone – Mediators of the continuous destruction of bone

• Interstitial macrophage: gut – represent the largest pool of tissue macrophages in the body. Recent evidence supports the notion that IMs perform important immune functions in the lung, notably in terms of innate immunoregulation.

• Kupffer cells: Liver- Initiate immune responses and hepatic tissue remodeling. Kupffer cells are the most abundant tissue macrophages as they constitute 80-90% of them.

• Microglia: Central nervous system – Elimination of old or dead neurons and control of immunity in the brain.

• Splenic macrophages: Spleen marginal zone, red and white pulp – Elimination of dysfunctional or old red blood cells.

The Role Of  Macrophages In Homeostasis

Macrophages play a pivotal role in the maintenance of tissue homeostasis and in tissue regeneration after injury.

In humans the tissue cellular turnover rate has been estimated to be more or less 1 million cells per second each day: the removal of apoptotic cells is constantly provided mainly by macrophages that reside in tissues, through an immunologically silent process known as efferocytosis.

One of the hallmarks of this process is represented by the release of anti-inflammatory cytokines that prevent the development of inflammation.

Defects in the clearance of apoptotic cells are directly linked to the development of inflammation and autoimmune diseases.

 When an inflammatory process is triggered by the perturbation of tissue homeostasis, bone-marrow derived monocytes that circulate in the blood-stream are attracted to the site of inflammation.

At the site of inflammation, monocytes differentiate into macrophages, which cooperate with resident cells for sustaining immunity or promoting resolution of inflammation and tissue regeneration.

The Role Of Macrophages In The Pathological Process

It is becoming increasingly accepted that macrophages play a crucial role in many diseases associated with chronic inflammation, including atherosclerosis, obesity, diabetes, cancer, skin diseases, and even neurodegenerative diseases.

It is therefore not surprising that macrophages in human diseases have gained significant interest during the last few years.

Macrophage activation syndrome is caused by the effects of massive macrophage activation.

Atherosclerosis is a chronic disease starting with the entry of monocytes into the subendothelium and the subsequent differentiation into macrophages.

Macrophages are the major immune cells in atherosclerotic plaques and are involved in the dynamic progression of atherosclerotic plaques.

Accumulating evidence has demonstrated that resident macrophages can proliferate under microenvironment stimuli and dominate plaque macrophage accumulation in all stages of atherosclerosis.

Hepatic macrophage populations include different types of cells with plastic properties that can differentiate into diverse phenotypes to modulate their properties in response to different stimuli.

They often regulate the activity of other cells and play an important role in many hepatic diseases. In response to those pathological situations, they are activated, releasing cytokines and chemokines; they may attract circulating monocytes and exert functions that can aggravate the symptoms.

Adenoviruses, HIV, and the bacteria that cause tuberculosis are examples of microbes that cause disease by infecting macrophages.

Macrophages in fat tissue can cause inflammation which induces adipose cells to become resistant to insulin. This can lead to the development of diabetes.

Chronic inflammation caused by macrophages can also contribute to the development and growth of cancer cells

Macrophage Vs. Monocyte – What Is The Difference?

The main difference between monocyte and macrophage is that monocytes are the precursors of some of the macrophages whereas macrophages are the professional phagocytes, which engulf pathogens invading the body.

Monocytes and macrophages are two types of cells found in the immune system of organisms. They are considered as the front line of host defense.

Monocytes are bean-shaped small cells whereas macrophages are irregular-shaped large cells. Both monocytes and macrophages are capable of secreting cytokines and chemokines.

What Is A Monocyte?

Monocytes are a type of immune cells found in blood; they are capable of migrating to tissues by differentiating into macrophages. Monocytes are a kind of white blood cells, produced in bone marrow.

They are capable of being differentiated into dendritic cells as well. Monocytes are involved in the innate immunity of an organism, serving as the front line defense of the host.

They also allow the adaptive immune system to be activated by triggering an inflammatory response.

Monoblasts in bone marrow are the precursors of monocytes. After releasing into the bloodstream, monocytes circulate for three days along with the blood prior to differentiating into either macrophages or dendritic cells.

Monocytes are the largest type of cells in the blood. Three types of monocytes are found in blood, depending on the receptors found on the surface of the cells.

Classical monocytes contain the surface receptor, CD14. Non-classical monocytes contain CD16 along with the CD14. Intermediate monocytes contain CD14 and low levels of CD16 receptors on the cell surface.

Half of the adult monocytes are stored in the spleen. Monocytes contain granules in the cytoplasm, which contain necessary enzymes for the digestion of engulfed pathogens.

They contain bean-shaped, uni-lobed nuclei. Monocytes count for 2-10% of total white blood cell count in blood. 

The monocyte is a spherical cell with prominent surface ruffles and blebs when examined by scanning electron microscopy.

As the monocyte enters the tissue and differentiates into a macrophage, the cell volume and number of cytoplasmic granules increase. Cell shape varies, depending on the tissue in which the macrophage resides (e.g., lung, liver, spleen, brain).

A characteristic feature of macrophages is their prominent electron-dense membrane-bound lysosomes, which can be seen fusing with phagosomes to form secondary lysosomes.

The latter contain ingested cellular and noncellular material in different stages of degradation.

A broad range of surface receptors for many ligands, including the Fc portion of immunoglobulin, complement proteins, cytokines, chemokines, lipoproteins, and others, are on the cell surface. 

Macrophages differ in appearance, biochemistry, and function based on the environment in which they mature from monocytes.

These differences are exemplified by the diversity among dendritic cells of lymph nodes, histiocytes of connective tissue, osteoclasts of bone, Kupffer cells of liver, microglia of the central nervous system, and macrophages of the serosal surfaces, each fashioned to meet the local needs of the mononuclear phagocyte system, which plays a role in inflammation and host defense against microbes.

Modern cell biologic methods refined our knowledge of surface receptors, endocytosis, and lysosomal degradation, with emphasis on membrane flow and secretion. 

These pioneering studies culminated in the discovery of dendritic cells as potent, specialized antigen-presenting cells.

subsequent development of monoclonal antibodies and molecular cloning of surface proteins and cytokines, followed by microarray analysis and genomics, provided the sensitive and specific tools to analyze macrophage functions in vitro and in vivo. 

Their Core Differences

Presence

• Monocyte: Monocytes are found in the blood.
• Macrophage: Macrophages are found in the extracellular fluid.

Diameter

• Monocyte: Diameter of a monocyte is around 7.72-9.99  μm.
• Macrophage: Diameter of a macrophage is 21 μm.

Function

• Monocyte: Monocytes are macrophages.
• Macrophage: Macrophages phagocytize cell debris and foreign material like bacteria and virus.

Receptors

• Monocyte: Monocytes contain CD14 and CD16 on the surface of the cell.
• Macrophage: Macrophages contain CD14, Cd11b, CD68, MAC-1 and -3, EMR1 and Lysozyme M on the surface of the cells.

Function

• Monocyte: Monocytes are involved in the innate immunity by differentiating into macrophages. They are involved in the adaptive immunity by secreting cytokines and chemokines.
• Macrophage: Macrophages are involved in the innate immunity as well as the adaptive immunity by presenting the antigens of the foreign bodies on their MHC complex.

Monocytes and macrophages are two immune system cells, involved in the innate immunity as well as the adaptive immunity. Monocytes are found in blood.

While responding to inflammation, monocytes migrate to the extracellular fluid, which surrounds the inflammatory tissue, differentiating into macrophages.

Macrophages phagocytize pathogens and destroy them by phagocytosis during innate immunity. Innate immunity generates non-specific responses while destroying pathogens.

Macrophages present antigens of the destroyed pathogens in order to be identified by T helper cells. T helper cells then activate B lymphocytes, producing specific antigens for a particular pathogen.

Specific antigens are involved in adaptive immunity. Macrophages in different organs are involved in clearing off defective cells in the body.

However, the main difference between monocytes and macrophages is their location and function in immunity.

Macrophages Vs. Neutrophils – What Is The Difference?

Neutrophils and macrophages are two types of blood cells found in mammals. Both macrophages and neutrophils are involved in the innate immunity by serving as phagocytes, which engulf and destroy pathogens, dead cells, and dell debris.

But, they differ in their morphology and function in the body. The main difference between neutrophils and macrophages is that neutrophils are granulocytes which work as phagocytes only in circulation.

Whereas macrophages are agranulocytes which work as phagocytes inside the tissues.

What Are Neutrophils?

Neutrophils are the most abundant white blood cell type in the blood. They contain a granular cytoplasm as well as a nucleus with two to five lobes. A normal adult produces around 100 billion neutrophils daily.

Neutrophils are one of the first cells to migrate into the site of an inflammation, following the cytokine signals produced by the infected cells. This process of migration is called chemotaxis.

Neutrophils show an ameboid movement by extending long projections called pseudopodia. They engulf microorganisms, cell debris as well as dead cells by active phagocytosis.

The enzymes stored in the granules are involved in the digestion of phagocytized particles. During the metabolism inside the granules, hydrogen peroxide is produced.

The phagocytized particles are encased in a vacuole to which the hydrogen peroxide is released and by the action of hydrogen peroxide, particles are destroyed.

The depletion of granules is referred to as degranulation. Neutrophil numbers increase due to acute infections. The abnormal lower numbers of neutrophils are referred to as neutropenia.

Similarities Between Neutrophils And Macrophages

• Both neutrophils and macrophages originate from the bone marrow.
• Both of them are professional phagocytes, which are involved in the innate immunity by phagocytosis.
• Both detect pathogens and help to initiate inflammation.
• Both serve as antigen presenting cells.
• Both are capable of enhancing inflammation as well as limit or suppress inflammation.
• They promote tissue repair.
• Neither neutrophils or macrophages are capable of degrading or detoxifying components of animal venom.

Difference Between Neutrophils And Macrophages

Definition

• Neutrophils: Neutrophil is a granular leukocyte, consisting of a nucleus with three to five lobes.
• Macrophages: Macrophage is a large white blood cell that engulfs foreign particles in the body.

Shape Of The Nucleus

• Neutrophils: Neutrophils have a multi-lobed nucleus.
• Macrophages: Macrophages have a large, rounded shape nucleus.

Granulocytes/Agranulocytes

• Neutrophils: Neutrophils are granulocytes.
• Macrophages: Macrophages are agranulocytes.

Makeup

• Neutrophils: Neutrophils make up 50-70% of circulating white blood cells.
• Macrophages: Monocytes make up 2-8% of circulating white blood cells.

Difference In Phenotype

• Neutrophils: Neutrophils consist of Ly6G+, and MPO+ receptors on the cell membrane.
• Macrophages: Macrophages consist of EMR1+, CD107b+ (Mac-3+), and CD68+ receptors on the cell membrane.    

Site Of Maturation

• Neutrophils: Neutrophils mature in the bone marrow.
• Macrophages: Macrophages mature in tissues.

Mature Cells In Circulation

• Neutrophils: Mature neutrophils are found in circulation.
• Macrophages: Very few macrophages can be found in circulation.

Mature Cells Recruited Into Tissues From Circulation

• Neutrophils: During innate and acquired immunity, mature neutrophils migrate from circulation into tissues.
• Macrophages: Only immature monocytes migrate from the circulation into tissues.

Normal Residence Of Mature Cells In Connective Tissues

• Neutrophils: Mature neutrophils do not reside in connective tissues.
• Macrophages: Mature macrophages normally reside in connective tissues.

Phenotypically Distinct Sub-Populations In Different Tissues

• Neutrophils: No phenotypic variations are observed in neutrophils.
• Macrophages: Macrophages consist of phenotypically varied sub-populations in distinct tissues.

Proliferative Ability Of Mature Cells

• Neutrophils: Generally mature neutrophils are incapable of proliferating.
• Macrophages: M2 macrophages are capable of proliferating in certain circumstances.

Lifespan

• Neutrophils: The lifespan of neutrophils is typically several days.
• Macrophages: The lifespan of macrophages is weeks to months.

Role

• Neutrophils: Neutrophils are the first to attack bacteria at the site of infection. The action of neutrophils forms pus.
• Macrophages: Monocytes from the circulation enter the peripheral tissues, becoming tissue macrophages, which engulf large particles and pathogens.

Neutrophils and macrophages are professional phagocytes found in the body. Both of them are involved in destroying the pathogens and unwanted particles like cell debris and dead cells.

Neutrophils originate in bone marrow and mature during circulation. Macrophages are derived from monocytes, which also originate in the bone marrow.

Monocytes migrate into tissues and become macrophages. This is the main difference between neutrophils and macrophages.

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