Monocytosis is the state of excess monocytes in the peripheral blood. It may be indicative of various disease states.

Examples of processes that can increase a monocyte count include:

- chronic inflammation

- stress response

- Cushing's syndrome (hyperadrenocorticism)

- immune-mediated disease

- granulomatous disease

- atherosclerosis

- necrosis

- red blood cell regeneration

- viral fever

- sarcoidosis

A high count of CD14+CD16++ monocytes is found in severe infection (sepsis)

In the field of atherosclerosis high numbers of the CD14++CD16+ intermediate monocytes were shown to be predictive of cardiovascular events in at risk populations.

An increase in eosinophils, i.e., the presence of more than 500 eosinophils/microlitre of blood is called an eosinophilia, and is typically seen in people with a parasitic infestation of the intestines; autoimmune and collagen vascular disease (such as rheumatoid arthritis) and Systemic lupus erythematosus; malignant diseases such as eosinophilic leukemia, clonal hypereosinophilia, and Hodgkin's disease; lymphocyte-variant hypereosinophilia; extensive skin diseases (such as exfoliative dermatitis); Addison's disease and other causes of low corticosteroid production (corticosteroids suppress blood eosinophil levels); reflux esophagitis (in which eosinophils will be found in the squamous epithelium of the esophagus) and eosinophilic esophagitis; and with the use of certain drugs such as penicillin. But, perhaps the most common cause for eosinophilia is an allergic condition such as asthma. In 1989, contaminated L-tryptophan supplements caused a deadly form of eosinophilia known as eosinophilia-myalgia syndrome, which was reminiscent of the Toxic Oil Syndrome in Spain in 1981.

Eosinophils play an important role in asthma as the number of accumulated eosinophils corresponds to the severity of asthmatic reaction. Eosinophilia in mice models are shown to be associated with high interleukin-5 levels. Furthermore, mucosal bronchial biopsies conducted on patients with diseases such as asthma have been found to have higher levels of interleukin-5 leading to higher levels of eosinophils. The infiltration of eosinophils at these high concentrations causes an inflammatory reaction. This ultimately leads to airway remodelling and difficulty of breathing.

Eosinophils can also cause tissue damage in the lungs of asthmatic patients. High concentrations of eosinophil major basic protein and eosinophil-derived neurotoxin that approach cytotoxic levels are observed at degranulation sites in the lungs as well as in the asthmatic sputum.

Treatments used to combat autoimmune diseases and conditions caused by eosinophils include:

- corticosteroids – promote apoptosis. Numbers of eosinophils in blood are rapidly reduced

- monoclonal antibody therapy – e.g., mepolizumab or reslizumab against IL-5, prevents eosinophilopoiesis

- antagonists of leukotriene synthesis or receptors

- imatinib (STI571) – inhibits PDGF-BB in hypereosinophilic leukemia

Monoclonal antibodies such as dupilumab and lebrikizumab target IL-13 and its receptor, which reduces eosinophilic inflammation in pateints with asthma due to lowering the number of adhesion molecules present for eosinophils to bind to, thereby decreasing inflammation. Mepolizumab and benralizumab are other treatment options that target the alpha subunit of the IL-5 receptor, thereby inhibiting its function and reducing the number of developing eosinophils as well as the number of eosinophils leading to inflammation through antibody-dependent cell-mediated cytotoxicity and eosinophilic apoptosis.

Monocytopenia is a form of leukopenia associated with a deficiency of monocytes.

A very low count of these cells is found after therapy with immuno-suppressive glucocorticoids.

Also, non-classical slan+ monocytes are strongly reduced in patients with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), a neurologic disease associated

with mutations in the macrophage colony-stimulating factor receptor gene.

Macrophages (pronunciation: /ˈmakrə(ʊ)feɪdʒ/ | , from Greek "μακρός" ("makrós") = large, "φαγείν" ("phageín") = to eat) are a type of white blood cell that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the types of proteins specific to healthy body cells on its surface in a process called phagocytosis. These large phagocytes 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 rodent 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 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 by Élie Metchnikoff, a Russian zoologist, in 1884.

A histiocyte is an animal cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyte is a tissue macrophage or a dendritic cell (histio, diminutive of histo, meaning "tissue", and cyte, meaning "cell").

Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self and foreign lipids and glycolipids. They constitute only approximately 0.1% of all blood T cells. Natural killer T cells should not be confused with natural killer cells.

Infection of macrophages in joints is associated with local inflammation during and after the acute phase of "Chikungunya" (caused by CHIKV or Chikungunya virus).

Agranulocytes, also known as mononuclear leukocytes, are white blood cells with a one-lobed nucleus. They are characterized by the absence of granules in their cytoplasm, which distinguishes them from granulocytes. Normal hematologic blood values of MLs are about 35% of all white blood cells. The 2 types of agranulocytes in the blood circulation are lymphocytes and monocytes. A third type of agranulocyte, the macrophage, is formed in the tissue when monocytes leave the circulation and differentiate into macrophages.

Lymphocytes are much more common in the lymphatic system, and include natural killer T-cells. The blood has three types of lymphocytes: B cells, T cells and natural killer cells (NK cells). B cells make antibodies that bind to pathogens to enable their destruction. CD4+ (helper) T cells co-ordinate the immune response (they are what becomes defective in an HIV infection). CD8+ (cytotoxic) T cells and natural killer cells are able to kill cells of the body that are infected by a virus. T cells are crucial to the immune response because they possess a unique 'memory' system which allows them to remember past invaders and prevent disease when a similar invader is encountered again.

Monocytes share the "vacuum cleaner" (phagocytosis) function of neutrophils, but are much longer lived as they have an additional role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed, or so that an antibody response may be mounted. Monocytes are also known as macrophages after they migrate from the bloodstream and enter tissue.

Other white blood cells which are not agranulocytes are mainly the granulocytes: neutrophils, eosinophils and basophils.

The term "NK T cells" was first used in mice to define a subset of T cells that expressed the natural killer (NK) cell-associated marker NK1.1 (CD161). It is now generally accepted that the term "NKT cells" refers to CD1d-restricted T cells, present in mice and humans, some of which coexpress a heavily biased, semi-invariant T-cell receptor and NK cell markers.

Research into AM functionality has been on the rise since AMs are one of the first lines of a defense against invasive pathogens. One of the most prominent fields is investigating liposomes as deliverers of antibiotics for treatment of respiratory intracellular infections. Intracellular parasites, such as M. tuberculosis, C. pneumoniae, L. monocytogenes, L. pneumophila, and F. tularensis, (to name a few) are taken up by AMs via phagocytosis, but are resistant to the biocidal mechanisms of AMs and can survive intracellularly, thus inducing severe respiratory infections. Pulmonary tuberculosis is caused by M. tuberculosis, and is now a major infectious disease worldwide and its incidence is increasing, especially in association with the AIDS pandemic. For sterilization of intracellular parasites in AMs, antibiotics are normally given orally or intravenously, but much of the antibiotics disperse to many different tissues, diminishing its effectiveness. Pulmonary administration of mannosylated liposomes is a much more direct, efficient route in targeting AMs; it enhances antimicrobial effect, reduces the dosage needed, and avoids unnecessary distribution to the blood. Since mannose receptors are exclusively expressed on the surface of AM, mannosylation of liposomes is an appealing approach to cell-selective targeting to AM. The efficacy of pulmonary administration of ciprofloxacin (CPFX) incorporated into mannosylated liposomes (mannosylated CPFX-lipososomes) was examined in rats, and determined to be an efficient means to target AMs.

Histiocytes are derived from the bone marrow by multiplication from a stem cell. The derived cells migrate from the bone marrow to the blood as monocytes. They circulate through the body and enter various organs, where they undergo differentiation into histiocytes, which are part of the mononuclear phagocytic system (MPS).

However, the term "histiocyte" has been used for multiple purposes in the past, and some cells called "histocytes" do not appear to derive from monocytic-macrophage lines. (The term Histiocyte can also simply refer to a cell from monocyte origin outside the blood system, such as in a tissue (as in rheumatoid arthritis as palisading histiocytes surrounding fibrinoid necrosis of rheumatoid nodules).

Some sources consider Langerhans cell derivatives to be histiocytes. The Langerhans cell histiocytosis embeds this interpretation into its name.

Adipose tissue macrophages (abbr. ATMs) comprise tissue resident macrophages present in adipose tissue. Adipose tissue apart from adipocytes is composed of the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and variety of immune cells. The latter ones are composed of mast cells, eosinophils, B cells, T cells and macrophages. The number of macrophages within adipose tissue differs depending on the metabolic status. As discovered by Rudolph Leibel and Anthony Ferrante et al. in 2003 at Columbia University, the percentage of macrophages within adipose tissue ranges from 10% in lean mice and humans up to 50% in extremely obese, leptin deficient mice and almost 40% in obese humans. Increased number of adipose tissue macrophages correlates with increased adipose tissue production of proinflammatory molecules and might therefore contribute to the pathophysiological consequences of obesity (e.g. insulin resistance, type 2 diabetes).

Small image of an infected area of the body due to a reaction with an implant

Xanthogranulomatous osteomyelitis (XO) is a peculiar aspect of osteomyelitis characterized by prevalent histiocytic infiltrate and foamy macrophage clustering.

Microglia are the primary immune cells of the Central Nervous System, similar to peripheral macrophages. They respond to pathogens and injury by changing morphology and migrating to the site of infection/injury, where they destroy pathogens and remove damaged cells. As part of their response they secrete cytokines, chemokines, prostaglandins, and reactive oxygen species, which help to direct the immune response. Additionally, they are instrumental in the resolution of the inflammatory response, through the production of anti-inflammatory cytokines. Microglia have also been extensively studied for their harmful roles in neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Multiple sclerosis, as well as cardiac diseases, glaucoma, and viral and bacterial infections.

Foam cells are the fat-laden M2 macrophages that serve as the hallmark of early stage atherosclerotic lesion formation. They are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening.

Foam cell formation is triggered by a number of factors including the uncontrolled uptake of modified low density lipoproteins (LDL), the upregulation of cholesterol esterification and the impairment of mechanisms associated with cholesterol release. Foam cells are formed when circulating monocyte-derived cells are recruited to the atherosclerotic lesion site or fat deposits in the blood vessel walls. Recruitment is facilitated by the molecules P-selectin and E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). Monocytes are then able to penetrate the arterial wall as a result of impaired endothelial integrity which increases permeability. Once in the sub endothelium space, inflammation processes induce the differentiation of monocytes into mature macrophages. Macrophages are then able to internalize modified lipoproteins like βVLDL (beta very low density lipoprotein), AcLDL (acetylated low density lipoprotein) and OxLDL (oxidized low density lipoprotein), which are rich in cholesterol esters, through their binding to scavenger receptors (SR), CD36 and SR-A located on the macrophage surface. Coated-pit endocytosis, phagocytosis and pinocytosis are all responsible for lipoprotein internalization. Lipoproteins are transported to endosomes or liposomes for degradation, whereby the cholesteryl esters (CE) are hydrolyzed to unesterified free cholesterol (FC) by lysosomal acid lipase (LPL). Free cholesterol is transported to the endoplasmic reticulum where it is re-esterified by ACAT1 (acyl-CoA: cholesterol acyltransferase 1) and subsequently stored as cytoplasmic liquid droplets. These droplets are responsible for the foamy appearance of the macrophage and thus the name of foam cells. At this point, foam cells can either be degraded though the de-esterification and secretion of cholesterol, or can further promote foam cell development and plaque formation – a process that is dependent on the balance of free cholesterol and esterified cholesterol.

Low-density lipoprotein (LDL) and modified LDL cholesterol, also known as “bad” cholesterol, is contained by a foam cell - a marker of atherosclerosis. The uptake of LDL alone does not cause foam cell formation, however, the co-internalization of LDL with modified LDL in macrophages can result foam cell development. Modified LDL affects the intracellular trafficking and metabolism of native LDL, such that not all LDL need to be modified for foam cell formation when LDL levels are high.

Foam cell degradation or more specifically the breakdown of esterified cholesterols, is facilitated by a number of efflux receptors and pathways. Esterified cholesterol from cytoplasmic liquid droplets are once again hydrolyzed to free cholesterol by acid cholesterol esterase. Free cholesterol can then be secreted from the macrophage by the efflux to ApoA1 and ApoE discs via the ABCA1 receptor. This pathway is usually used by modified or pathological lipoproteins like AcLDL, OxLDL and βVLDL. FC can also be transported to a recycling compartment through the efflux to ApoA1 containing HDLs (high density lipoproteins) via aqueous diffusion or transport through the SR-B1 or ABCG1 receptors. While this pathway can also be used by modified lipoproteins, LDL derived cholesterol can only use this pathway to excrete FC. The differences in excretory pathways between types of lipoproteins is mainly a result of the cholesterol being segregated into different areas.

The maintenance of foam cells and the subsequent progression of plaque build-up is caused by the secretion of chemokines and cytokines from macrophages and foam cells. Foam cells secrete pro-inflammatory cytokines such as interleukins: IL-1, IL-6; tumour necrosis factor (TNF); chemokines: chemokines ligand 2, CCL5, CXC-chemokine ligand 1 (CXCL1); as well as macrophage retention factors. Macrophages within the atherosclerotic legion area have a decreased ability to migrate, which further promotes plaque formation as they are able to secrete cytokines, chemokines, reactive oxygen species (ROS) and growth factors that stimulate modified lipoprotein uptake and vascular smooth muscle cell (VSMC) proliferation. VSMC can also accumulate cholesteryl esters.

To summarize, in chronic hyperlipidemia, lipoproteins aggregate within the intima of blood vessels and become oxidized by the action of oxygen free radicals generated either by macrophages or endothelial cells. The macrophages engulf oxidized low-density lipoproteins (LDLs) by endocytosis via scavenger receptors, which are distinct from LDL receptors. The oxidized LDL accumulates in the macrophages and other phagocytes, which are then known as foam cells. Foam cells form the fatty streaks of the plaques of atheroma in the tunica intima of arteries.

Foam cells are not dangerous as such, but can become a problem when they accumulate at particular foci thus creating a necrotic centre of atherosclerosis. If the fibrous cap that prevents the necrotic centre from spilling into the lumen of a vessel ruptures, a thrombus can form which can lead to emboli occluding smaller vessels. The occlusion of small vessels results in ischemia, and contributes to stroke and myocardial infarction, two of the leading causes of cardiovascular-related death.

Foam cells are very small in size and can only be truly detected by examining a fatty plaque under a microscope after it is removed from the body, or more specifically from the heart. Detection usually involves the staining of sections of aortic sinus or artery with Oil Red O (ORO) followed by computer imaging and analysis; or from Nile Red Staining. In addition, flouresecnet microscopy or flow cytometry can be used to detect OxLDL uptake when OxLDL has been labeled with 1,1′-dioctadecyl-3,3,3′3′-tetra-methylindocyanide percholorate (DiL-OxLDL).

Autoimmunity occurs when the body starts attacking itself. The link between atherosclerosis and autoimmunity is plasmacytoid dendritic cells (pDCs). PDCs contribute to the early stages of the formation of atherosclerotic lesions in the blood vessels by releasing large quantities of type 1 interferons (INF). Stimulation of pDCs leads to an increase of macrophages present in plaques. However, during later stages of lesion progression, pDCs have been shown to have a protective effect by activating T cells and Treg function; leading to disease supression.

Foam cells may form around leaked silicone from breast implants, inhaled organic antigens and some drugs.

The Xanthogranulomatous Process (XP), also known as Xanthogranulomatous Inflammation is a form of acute and chronic inflammation characterized by an exuberant clustering of foamy macrophages among other inflammatory cells. Localization in the kidney and renal pelvis has been the most frequent and better known occurrence followed by that in the gallbladder but many others have been subsequently recorded. The pathological findings of the process and etiopathogenetic and clinical observations have been reviewed by Cozzutto and Carbone.

The granulomatous tissue largely comprises foam cells of monocyte/macrophage origin positive for KP1, HAM56, CD11b and CD68. Neutrophils, hemorrhagic foci and numerous plasma cells are additional findings. Staphylococcus aureus was isolated in the case reported by Kamat et al. A delayed type hypersensitivity reaction in cell-mediated immunity has been suggested in this type of infiltrate that is composed of macrophages and T cells. T cells are represented by a mixture of CD4+ and CD8+ lymphocytes. Macrophages and lymphocytes show marked expression of HLA-DR antigen.

Arguably XO is the bone localization of the xanthogranulomatous process occurring in several other locations.

Macrophages within tumor stroma, so called tumor-associated macrophages (TAMs) promote tumor growth and metastasis. Tumor-associated macrophage infiltration correlates with poor prognosis in patients with breast, cervix, bladder and brain cancers. Pathophysiological interaction between tumor-associated macrophages and surrounding cells, such as endothelial cells promote tumor progression. In 1971, Judah Folkman proposed that angiogenesis plays essential role in tumor growth. Macrophages secrete many pro-angiogenic factors including vascular endothelial growth factor (VEGF), TNF-α, granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-1 and IL-6. Additionally it has been shown that adipose tissue surrounding certain tumors or metastases to the lymph nodes, which are embedded in adipose tissue, fuels tumor growth by serving as a depot for adipose tissue macrophages that stumulate angiogenesis and resemble TAMs.

An alveolar macrophage (or dust cell) is a type of macrophage found in the pulmonary alveolus, near the pneumocytes, but separated from the wall.

Activity of the alveolar macrophage is relatively high, because they are located at one of the major boundaries between the body and the outside world. They are responsible for removing particles such as dust or microorganisms from the respiratory surfaces.

Alveolar macrophages are frequently seen to contain granules of exogenous material such as particulate carbon that they have picked up from respiratory surfaces. Such black granules may be especially common in smoker's lungs or long-term city dwellers.

Inhaled air may contain particles or organisms which would be pathogenic. The respiratory pathway is a prime site for exposure to pathogens and toxic substances. The respiratory tree, comprising the larynx, trachea, and bronchioles, is lined by ciliated epithelia cells that are continually exposed to harmful matter. When these offensive agents infiltrate the superficial barriers, the body's immune system responds in an orchestrated defense involving a litany of specialized cells which target the threat, neutralize it, and clean up the remnants of the battle.

Deep within the lungs exists its constituent alveoli sacs, the sites responsible for the uptake of oxygen and excretion of carbon dioxide. There are three major alveolar cell types in the alveolar wall (pneumocytes):

- Type I pneumocyte (Squamous Alveolar) cells that form the structure of an alveolar wall.

- Type II pneumocyte (Great Alveolar) cells that secrete pulmonary surfactant to lower the surface tension of water and allows the membrane to separate, thereby increasing the capability to exchange gases. Surfactant is continuously released by exocytosis. It forms an underlying aqueous protein-containing hypophase and an overlying phospholipid film composed primarily of dipalmitoyl phosphatidylcholine.

- Macrophages that destroy foreign material, such as bacteria.

Type 1 and type 2 pneumocytes. Type 1 pneumocytes (or membranous pneumocytes) form the structure of the alveolus and are responsible for the gas exchange in the alveolus. Type 1 pneumocytes are squamous epithelial cells which are characterized by a superficial layer consisting of large, thin, scale-like cells; they also cover 95% of the alveolar surface, although they are only half as numerous as Type 2 pneumocytes. Type 2 pneumocytes are important in that they can proliferate and differentiate into type 1 pneumocytes, which cannot replicate and are susceptible to a vast numbers of toxic insults. Type 2 pneumocytes are also important because they secrete pulmonary surfactant(PS), which consists 80–90% of phospholipids [(phosophatidylcholine(PC), phosphatidyglycerol(PG), phosphaditylinositol (PI)] and 5-10% of surfactant proteins (SP-A, SP-B, SP-C, AND SP-D). PS is synthesized as lamellar bodies, which are structures consisting of closely packed bilayers that are secreted and then undergo transformation into a morphological form called tubular myelin. PS plays an important role in maintaining normal respiratory mechanics by reducing alveolar surface tension. By lowering alveolar surface tension, PS reduces the energy required to inflate the lungs, and reduces the likelihood of alveolar collapse during expiration. Loosely attached to these alveoli sacs are the alveolar macrophages that protect the lungs from a broad array of microbes and aerosols by devouring and ingesting them through phagocytosis.

Alveolar macrophages are phagocytes that play a critical role in homeostasis, host defense, the response to foreign substances, and tissue remodeling. Since alveolar macrophages are pivotal regulators of local immunological homeostasis, their population density is decisive for the many processes of immunity in the lungs. They are highly adaptive components of the innate immune system and can be specifically modified to whatever functions needed depending on their state of differentiation and micro-environmental factors encountered. Alveolar macrophages release numerous secretory products and interact with other cells and molecules through the expression of several surface receptors. Alveolar macrophages are also involved in the phagocytosis of apoptotic and necrotic cells that have undergone cell-death. They must be selective of the material that is phagocytized because normal cells and structures of the body must not be compromised. To combat infection, the phagocytes of the innate immune system facilitates many pattern recognition receptors (PRR) to help recognize pathogen-associated molecular patterns (PAMPs) on the surface of pathogenic microorganisms. PAMPs all have the common features of being unique to a group of pathogens but invariant in their basic structure; and are essential for pathogenicity(ability of an organism to produce an infectious disease in another organism). Proteins involved in microbial pattern recognition include mannose receptor, complement receptors, DC-SIGN, Toll-like receptors(TLRs), the scavenger receptor, CD14, and Mac-1. PRRs can be divided into three classes:

1. signaling PRRs that activate gene transcriptional mechanisms that lead to cellular activation,

2. endocytic PRRs that function in pathogen binding and phagocytosis, and

3. secreted PRRs that usually function as opsonins or activators of complement.

The recognition and clearance of invading microorganisms occurs through both opsonin-dependent and opsonin–independent pathways. The molecular mechanisms facilitating opsonin-dependent phagocytosis are different for specific opsonin/receptor pairs. For example, phagocytosis of IgG-opsonized pathogens occurs through the Fcγ receptors (FcγR), and involves phagocyte extensions around the microbe, resulting in the production of pro-inflammatory mediators. Conversely, complement receptor-mediated pathogen ingestion occurs without observable membrane extensions (particles just sink into the cell) and does not generally results in an inflammatory mediator response.

Following internalization, the microbe is enclosed in a vesicular phagosome which then undergoes fusion with primary or secondary lysosomes, forming a phagolysosome. There are various mechanisms that lead to intracellular killing; there are oxidative processes, and others independent of the oxidative metabolism. The former involves the activation of membrane enzyme systems that lead to a stimulation of oxygen uptake (known as the respiratory burst), and its reduction to reactive oxygen intermediates (ROIs), molecular species that are highly toxic for microorganisms. The enzyme responsible for the elicitation of the respiratory burst is known as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which is composed of five subunits. One component is a membrane cytochrome made up of two protein subunits, gp91phox and p22phox; the remaining three components are cytosolic-derived proteins: p40phox, p47phox, and p67phox. NADPH oxidase exists in the cytosol of the AM when in a quiescent state; but upon activation, two of its cytosolic components, p47phox and p67phox, have their tyrosine and serine residues phosphorylated, which are then able to mediate translocation of NADPHox to the cytochrome component, gp91phox/p22phox, on the plasma membrane via cytoskeletal elements.

Compared to other phagocytes, the respiratory burst in AM is of a greater magnitude. Oxygen-independent microbicidal mechanisms are based on the production of acid, on the secretion of lysozymes, on iron-binding proteins, and on the synthesis of toxic cationic polypeptides. Macrophages possess a repertoire of antimicrobial molecules packaged within their granules and lysosomes. These organelles contain a plethora of degradative enzymes and antimicrobial peptides that are released into the phagolysosome, such as proteases, nucleases, phosphatases, esterases, lipases, and highly basic peptides. Moreover, macrophages possess a number of nutrient deprivation mechanisms that are used to starve phagocytosed pathogens of essential micronutrients. Certain microorganisms have evolved countermeasures which enable them to evade being destroyed by phagocytes. Although lysosomal-mediated degradation is an efficient means by which to neutralize an infection and prevent colonization, several pathogens parasitize macrophages, exploiting them as a host cell for growth, maintenance and replication. Parasites like Toxoplasma gondii and mycobacteria are able to prevent fusion of phagosomes with lysosomes, thus escaping the harmful action of lysosomal hydrolases. Others avoid lysosomes by leaving the phagocytic vacuole, to reach the cytosolic matrix where their development is unhindered. In these instances, macrophages may be triggered to actively destroy phagocytosed microorganisms by producing a number of highly toxic molecules and inducing deprivational mechanism to starve it. Finally, some microbes have enzymes to detoxify oxygen metabolites formed during the respiratory burst.

When insufficient to ward off the threat, alveolar macrophages can release proinflammatory cytokines and chemokines to call forth a highly developed network of defensive phagocytic cells responsible for the adaptive immune response.

The lungs are especially sensitive and prone to damage, thus to avoid collateral damage to type 1 and type II pneumocytes, alveolar macrophages are kept in a quiescent state, producing little inflammatory cytokines and displaying little phagocytic activity, as evidenced by downregulated expression of the phagocytic receptor Macrophage 1 antigen (Mac-1). AMs actively suppress the induction of two of the immunity systems of the body: the adaptive immunity and humoral immunity. The adaptive immunity is suppressed through AM’s effects on interstitial dendritic cells, B-cells and T-cells, as these cells are less selective of what they destroy, and often cause unnecessary damage to normal cells. To prevent uncontrolled inflammation in the lower respiratory tract, alveolar macrophages secrete nitric oxide, prostaglandins, interleukin-4 and -10(IL-4, IL-10), and transforming growth factor-β (TGF-β).

Microglia are a type of neuroglia (glial cell) located throughout the brain and spinal cord. Microglia account for 10–15% of all cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune defence in the central nervous system (CNS). Microglia (and other neuroglia including astrocytes) are distributed in large non-overlapping regions throughout the CNS. Microglia are key cells in overall brain maintenance—they are constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents. Since these processes must be efficient to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS. This sensitivity is achieved in part by the presence of unique potassium channels that respond to even small changes in extracellular potassium.

The brain and spinal cord, which make up the CNS, are not usually accessed directly by pathogenic factors in the body's circulation due to a series of endothelial cells known as the blood–brain barrier, or BBB. The BBB prevents most infections from reaching the vulnerable nervous tissue. In the case where infectious agents are directly introduced to the brain or cross the blood–brain barrier, microglial cells must react quickly to decrease inflammation and destroy the infectious agents before they damage the sensitive neural tissue. Due to the unavailability of antibodies from the rest of the body (few antibodies are small enough to cross the blood–brain barrier), microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells.

A foreign-body giant cell is a collection of fused macrophages (giant cell) which are generated in response to the presence of a large foreign body. This is particularly evident with implants that cause the body chronic inflammation and foreign body response.

This reaction to the implant causes damages to the infected area, leaving the exterior surface with scars.

The nuclei are arranged in a disorganized manner. The nuclei in this cell are centrally placed and overlap each other. This is in contrast to a Langhans giant cell, where the nuclei are arranged on the border.

Foreign body cells can detect and eliminate

bacteria caught within the body, by sensing the unique sugar coating that are

on the invading prokaryotes. These macrophage cells are one of a few

phagocytic cells, but not the first to come to an injury site, and tend to

linger from anytime between days to weeks. There has been some research done on other variations of

giant calls with different functions.

As one route to reducing TAMs CSF1R inhibitors have been developed as a possible cancer therapy and many are in early clinical trials. CSF1R inhibitors in clinical trials include : Pexidartinib, PLX7486, ARRY-382, JNJ-40346527, BLZ945, Emactuzumab, AMG820, IMC-CS4. (MCS110 is a CSF1 inhibitor)

Another CSF1R inhibitor that targets/depletes TAMs is Cabiralizumab (cabira; FPA-008) which is a monoclonal antibody and is in early clinical trials for metastatic pancreatic cancer.