Introduction to Macrophages
- Macrophages are a type of white blood cell of the immune system.
- They engulf and digest pathogens, cancer cells, microbes, cellular debris, and foreign substances.
- Macrophages are involved in phagocytosis, which helps defend the body against infection and injury.
- They are found in all tissues and patrol for potential pathogens.
- Macrophages have various forms and names in different parts of the body.

Types and Development of Macrophages
- Macrophages can be classified as M1 macrophages, M2 macrophages, and regulatory macrophages.
- M1 macrophages increase inflammation and stimulate the immune system.
- M2 macrophages decrease inflammation and encourage tissue repair.
- Macrophages have different metabolic abilities depending on their type.
- Macrophages in healthy tissues can derive from circulating monocytes or be established before birth.
- Macrophages that accumulate at diseased sites typically derive from circulating monocytes.
- Monocytes enter damaged tissue and become macrophages through leukocyte extravasation.
- Macrophages can populate certain organs through proliferation.
- Macrophages have a longer lifespan compared to neutrophils.

Functions and Role in Innate Immune Response
- Macrophages are specialized in removing dying or dead cells and cellular debris.
- They play a crucial role in chronic inflammation and the early stages of inflammation.
- Macrophages can phagocytize neutrophils and foreign materials, such as pathogens.
- When a pathogen is ingested, it becomes trapped in a phagosome and is digested by enzymes.
- Macrophages are among the first cells to respond to a pathogen invasion.
- Tissue resident macrophages are among the first cells to respond to a pathogen invasion.
- They phagocytose incoming antigens and secrete proinflammatory cytokines.
- Phagocytosis of pathogens is an important function of macrophages.
- Macrophages can internalize antigens through receptor-mediated phagocytosis.
- They can also secrete proinflammatory cytokines to induce inflammation and recruit other immune cells.

Macrophage Recruitment of Immune Cells
- Macrophages recruit neutrophils to the infection site through chemokines such as CXCL1, CXCL2, and CXCL8.
- Other immune cells recruited by macrophages include monocytes, dendritic cells, natural killer cells, basophils, eosinophils, and T cells.
- Chemokines such as CCL2, CCL4, CCL5, CXCL8, CXCL9, CXCL10, and CXCL11 are involved in the recruitment of these immune cells.
- Macrophages, along with dendritic cells, help activate natural killer (NK) cells through secretion of type I interferons (IFN-α and IFN-β) and IL-12.
- IFN-γ produced by NK cells enhances the innate immune response by inducing a more aggressive phenotype in macrophages.

Macrophages and Adaptive Immunity
- Macrophages are professional antigen presenting cells (APC) that present peptides from phagocytosed antigens on MHC II molecules.
- Macrophages interact mostly with previously activated T helper cells or tissue resident memory T cells.
- Macrophages provide both signals required for T helper cell activation: antigen presentation through MHC II molecules and co-stimulatory signals through CD80 and CD86 molecules.
- These interactions allow T helper cells to achieve full effector function and receive survival and differentiation signals.
- Macrophages in lymphoid tissues are involved in preventing antigen entry into the blood and clearing debris from apoptotic lymphocytes.
- Macrophages can achieve different activation phenotypes through interactions with different subsets of T helper cells.
- The two major phenotypes are classically activated macrophages (M1 macrophages) and alternatively activated macrophages (M2 macrophages).
- M1 macrophages are proinflammatory, while M2 macrophages are mostly anti-inflammatory.
- T helper cells of the T1 subset play a role in classical macrophage activation against intracellular pathogens.
- Interaction between T1 cells and macrophages leads to the secretion of IFN-γ and upregulation of CD40 expression, activating macrophages and enhancing their ability to kill intracellular pathogens.

Macrophage (Wikipedia)

For the ecological classification, see Macrophage (ecology).

Macrophages (abbreviated as Mφ, MΦ or MP) (Greek: large eaters, from Greek μακρός (makrós) = large, φαγεῖν (phagein) = to eat) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.

Macrophage
Cytology of a macrophage with typical features. Wright stain.
Details
Pronunciation	/ˈmakrə(ʊ)feɪdʒ/
System	Immune system
Function	Phagocytosis
Identifiers
Latin	Macrophagocytus
Acronym(s)	Mφ, MΦ
MeSH	D008264
TH	H2.00.03.0.01007
FMA	63261
Anatomical terms of microanatomy [edit on Wikidata]

Macrophages are found in essentially all tissues, where they patrol for potential pathogens by amoeboid movement. They take various forms (with various names) throughout the body (e.g., histiocytes, Kupffer cells, alveolar macrophages, microglia, and others), but all are part of the mononuclear phagocyte system. Besides phagocytosis, they play a critical role in nonspecific defense (innate immunity) and also help initiate specific defense mechanisms (adaptive immunity) by recruiting other immune cells such as lymphocytes. For example, they are important as antigen presenters to T cells. In humans, dysfunctional macrophages cause severe diseases such as chronic granulomatous disease that result in frequent infections.

Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines. Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages. This difference is reflected in their metabolism; M1 macrophages have the unique ability to metabolize arginine to the "killer" molecule nitric oxide, whereas M2 macrophages have the unique ability to metabolize arginine to the "repair" molecule ornithine. However, this dichotomy has been recently questioned as further complexity has been discovered.

Human macrophages are about 21 micrometres (0.00083 in) in diameter and are produced by the differentiation of monocytes in tissues. They can be identified using flow cytometry or immunohistochemical staining by their specific expression of proteins such as CD14, CD40, CD11b, CD64, F4/80 (mice)/EMR1 (human), lysozyme M, MAC-1/MAC-3 and CD68.

Macrophages were first discovered and named by Élie Metchnikoff, a Russian Empire zoologist, in 1884.