MACROPHAGES: CHARACTERISTICS, FORMATION, TYPES, FUNCTIONS - BIOLOGY - 2025

The macrophages are phagocytic cells that belong to dedicated one of many types of cells present in the connective tissues. They exist as mobile and fixed cells, and are important effectors within the immune system.

They belong to the mononuclear phagocytic system, which includes, in addition to macrophages, monocytes, promonocytes and their precursor cells. The main function of the cells belonging to this system is to "clean" the blood, lymph and other tissues by ingesting or phagocytosis of different particles.

Macrophage phagocytizing a pathogenic fungal cell (Source: Carolina Coelho via Wikimedia Commons)

Macrophages are derived from the bone marrow, are distributed throughout the body and have different shapes and characteristics, which often depend on the tissue where they are found, their degree of differentiation and the age or time of life of the organism where they are study.

They are one of the most plastic cells of the hematopoietic system, since they are found in all tissues of the body and have different functions: they participate in development processes, in the maintenance of body homeostasis, in tissue repair and in the immune system.

One of its main functions is closely associated with the body's immune defense, since its phagocytic activity is regulated by components of the complement system and immunoglobulins (both components of the immune response system).

They were discovered more than a century ago, but have been defined as "ancestral" cells in the metazoan phylogeny. During its discovery, not only its phagocytic capacity was highlighted, but also its ability to distinguish between self and foreign, with which the concept of innate immunity was born.

Discovery

The first phagocytic cells were described from a study carried out with frogs in 1883 by the Russian zoologist Elie Metchnikoff, who not only described their function in defense against foreign agents, but also the ability of these cells to eliminate dying cells or senescent in the host and identify the own from the strange.

Metchnikoff was a leading researcher, listed as the father of modern immunology, who made important contributions to the development of immunology as a new discipline. Their findings also established a homological relationship between the invertebrate immune system and that of mammals.

With his description of phagocytes and phagocytic processes, this researcher, who was awarded a Nobel Prize more than a hundred years ago (in 1908), discovered one of the most intriguing mechanisms of innate immunity.

Their experiments consisted of "challenging" or "disturbing" larvae of a species of sea star with spines in order to stimulate their immune cells and study their reaction to the invasion of these foreign agents. With this, he observed the appearance of cells with special characteristics that "ate" these structures.

He coined the term "phagocytes" (from the Greek "payment" - devour- and "cytos" - cell-) to the cells that he observed, and to the process that carried out "phagocytosis", but the relevance of this discovery did not become evident until some years later, with the discoveries of Paul Ehrlich related to humoral immunity and antibodies.

characteristics

Macrophage-like cells share many characteristics in the different multicellular organisms where they can be found. They are transported from their production sites to different parts of the body, in different ways depending on the existence of a blood system or not.

The most distinctive characteristics of macrophages include their phagocytic capacity, the mobility of many of them and their biosynthetic capacity, which is accompanied by a great diversity of gene expression patterns.

In their active state, they are extremely dynamic cells, with intense membrane traffic. Various processes of membrane fusion and fission occur in them, associated with endocytosis and phagocytosis.

These specialized cells can be classified as "long-lived" since they apparently live for long periods of time in the peripheral tissues of the body. Furthermore, they are continually replaced by the differentiation of their progenitor cells from the bone marrow, which can leave the circulation and enter the different connective tissues.

Since they are mobile cells, some macrophages have folds in their plasma membrane. When they are arranged to engulf large particles, they can fuse with other cells to form what some authors refer to as a "giant foreign body cell," a giant multinucleated macrophage.

When observed in the tissues of which they are part, these cells are organized in defined patterns, where each cell occupies its own territory, something like a “tissue within another tissue”.

Training

The mononuclear phagocytic system is a hematopoietic lineage that is derived from progenitor cells of the bone marrow. Compromised progenitors differentiate to form blood monocytes, which travel through the stream and enter tissues to become resident macrophages.

The formation of the mononuclear phagocytic system begins with the most “immature” cells, the promonocytes, which are the replicative cells that give rise to monocytes. The latter are those that leave the bone marrow and reach the bloodstream, where, in the next 8 hours, they grow and differentiate into mature monocytes.

In places where mature monocytes find “favorable” conditions for phagocytosis, they differ in what are known as resident macrophages, since they are not free in circulation. It is then that they are equipped with all the appropriate apparatus for the digestion of the particles to be phagocytosed.

Differentiation involves various changes: growth of the cell body (at least 5 times the size of the original monocyte), increase in the number and complexity of internal organelles, acquisition of phagocytic capacity (accumulation of hydrolytic enzymes), and secretion of soluble factors.

These cells are distributed in all regions of the body. Some have special preferences for certain tissues (fixed), while others retain their ability to move (amoeboid) and are free or wandering.

Histology

Macrophages have a highly variable morphology due, in large part, to their mobile condition, since they are able to move between and through different tissues. They are irregularly shaped, flattened, and often show pseudopodia-like processes for movement.

The cell body of macrophages can measure up to 30μm in diameter; and in its cytoplasm a single nucleus of irregular shape is observed, with one or two prominent fissures that give it the shape of a kidney and a dense region formed by heterochromatin.

They have various vacuoles that provide enzymes and adequate spaces to engulf particles such as microorganisms or cell debris. In addition, they have a variety of lysosomes, "phagosomes", multivesicular bodies and residual bodies; that is why, under the microscope light, they are said to have a "granular" cytoplasm.

Since they require the synthesis of a large quantity of hydrolytic enzymes to exert their function, these cells present a highly developed endoplasmic reticulum, as well as a prominent Golgi complex to exert the functions of vesicular transport of these enzymes.

A histiocyte (macrophage) engulfing blood cells (hematophagocytosis) (Source: Koenjo via Wikimedia Commons)

Macrophages possess cortical arrangements of actin microfilaments that are characteristic for these cell types; Numerous microtubules and intermediate filaments are also observed, which they use for their amoeboid movement and during phagocytic processes.

Since they are phagocytic cells, they can be distinguished by injecting special dyes (trypan blue, lithium carmine, or India ink), since these stains are phagocytic and stored in the cytoplasm in the form of granules.

Types

In the human body, macrophages are distinguished according to their location and their function. In this way the intestinal macrophages, the alveolar (in the lungs), the histiocytes (in the connective tissues), the Kupffer cells (in the liver), the mesangial cells (in the kidney), the microglial cells (in the the brain) and osteoclasts (in the bone).

Intestinal macrophages

This class of macrophage represents one of the most abundant macrophage populations in the body and represents the first line of defense (innate immune system). They are found in the subepithelial lamina propria.

They are in charge of regulating the inflammatory responses against bacteria and against the different antigens that may overcome the epithelial barrier. In addition, they protect the mucosa against dangerous pathogens and "purify" the system of dead cells and other foreign debris.

Intestinal macrophages possess special mechanisms that make them capable of distinguishing between non-pathogenic commensal microorganisms and dangerous invaders.

Alveolar macrophages

They are specialized macrophages that reside in the pulmonary alveoli, compartments with large environmental fluctuations, mainly related to the partial pressure of oxygen. They are one of the few cell populations found in these spaces, in addition to some lymphocytes.

Like other macrophages, they have important functions in the "cleaning" of apoptotic cells and other cellular debris. They are also involved in the purification of polluting particles that enter through the respiratory tract, and also participate in different immunological processes.

Histiocytes

The term "histiocyte" is commonly used to refer to all cells with macrophage-like characteristics and ancestry found in connective tissues.

That is, it refers to differentiated cells that come from the monocyte / macrophage lineages, including sinusoidal macrophages in the spleen, alveolar macrophages in the lungs, and Kupffer cells in the liver.

Like the other types of macrophages, histiocytes defend the body from invading microorganisms and unwanted organic or inorganic particles, and they also participate in the presentation of antigens to T lymphocytes as the initiation of the immune response.

Kupffer cells

They are a type of liver cell that is classified within the group of resident macrophages, and that are related to the cells of the sinusoidal lining, which is nothing more than a layer of cells that covers the sinusoids, large vascular spaces located between the plates. of hepatocytes that make up the liver lobules.

Viewing an electron micrograph of these cells will reveal multiple cytoplasmic projections, many mitochondria, a reduced endoplasmic reticulum, a small Golgi complex, and many lysosomes and endosomes.

These are considered to be "migratory garbage" cells, since they do not have intercellular connections with their neighboring cells.

Mesangial cells

Mesangial cells are cells resident in the glomeruli of the kidney, which are the sites in this organ where blood is filtered and urine is synthesized. Their main functions include the regulation of blood flow and phagocytosis, and they are involved in different kidney pathologies.

They have characteristics of modified smooth muscle cells, as they have inherent contractility, and are capable of producing cytokines and endocytizing macromolecules such as immune complexes.

Microglial cells

They represent 20% of the cells in the central nervous system and are morphologically, immunophenotypically and functionally related to cells of the monocyte / macrophage lineage.

They are activated in response to a wide variety of conditions or injuries in the brain and are responsible for defending against invading microorganisms.

Osteoclasts

Osteoclasts are cells belonging to bone tissue that are responsible for a process known as "bone resorption", which is essential for the homeostasis of this connective tissue, during and after osteogenesis.

Its functions are related to its ability to "hydrolyze" apoptotic or senescent cells that make up bone tissue through the secretion of lysosomal enzymes and other ions that participate in the process.

Features

Macrophages are highly plastic cells that are specialized in phagocytosis of foreign substances and invading microorganisms, damaged, old or senescent cells, and cellular debris, among others. They have also been shown to be involved in pinocytosis.

Certain types of macrophages have "specialized" phagocytic functions, such as bacterial phagocytosis that occurs after the recognition of special carbohydrate residues on bacterial cell walls by receptors on the surface of the macrophage known as C3.

In addition to their "sentinel" and "cleanup" functions, resident macrophages are capable of initiating acute inflammatory responses and vascular changes through their association with the microvasculature.

During these inflammatory responses, macrophages are activated by factors secreted by lymphocytes, which helps them increase their phagocytic capacity thanks to a kind of metamorphosis through which they acquire microvilli and lamellipodia (membrane extensions).

Some types of macrophages phagocytose antigens and present them to lymphocytes, thus they are directly involved in the cascades of immune responses. In addition, they secrete special factors that stimulate the division of T lymphocytes, the differentiation of B lymphocytes, etc.

Alveolar macrophages are the best example for the "non-phagocytic" functions of macrophages, since they can endocyte soot, asbestos, industrial gaseous pollutants, cigarette smoke and even cotton fibers.

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