Editing Inflammation (section)

== Cellular component ==
The ''cellular component'' involves [[leukocyte]]s, which normally reside in blood and must move into the inflamed tissue via ''extravasation'' to aid in inflammation.<ref name=":1" /> Some act as [[phagocyte]]s, ingesting bacteria, viruses, and cellular debris. Others release enzymatic [[granule (cell biology)|granules]] that damage pathogenic invaders. Leukocytes also release inflammatory mediators that develop and maintain the inflammatory response. In general, acute inflammation is mediated by [[granulocyte]]s, whereas chronic inflammation is mediated by mononuclear cells such as [[monocyte]]s and [[lymphocyte]]s.

=== Leukocyte extravasation ===
[[File:NeutrophilerAktion.svg|200px|thumb|right|Neutrophils migrate from blood vessels to the infected tissue via chemotaxis, where they remove pathogens through phagocytosis and degranulation]]
[[File:Immune response.svg|thumb|Inflammation is a process by which the body's white blood cells and substances they produce protect us from infection with foreign organisms, such as bacteria and viruses. The (phagocytes) white blood cells are a nonspecific immune response, meaning that they attack any foreign bodies. However, in some diseases, like arthritis, the body's defense system the immune system triggers an inflammatory response when there are no foreign invaders to fight off. In these diseases, called autoimmune diseases, the body's normally protective immune system causes damage to its own tissues. The body responds as if normal tissues are infected or somehow abnormal.]]
{{Main|Leukocyte extravasation}}
Various [[leukocyte]]s, particularly neutrophils, are critically involved in the initiation and maintenance of inflammation. These cells must be able to move to the site of injury from their usual location in the blood, therefore mechanisms exist to recruit and direct leukocytes to the appropriate place. The process of leukocyte movement from the blood to the tissues through the blood vessels is known as ''extravasation'' and can be broadly divided up into a number of steps:
# '''Leukocyte margination and endothelial adhesion:''' The white blood cells within the vessels which are generally centrally located move peripherally towards the walls of the vessels.<ref name=":0">{{Cite book |title=Muir's Textbook of Pathology |vauthors=Herrington S |publisher=CRC Press |year=2014 |isbn=978-1-4441-8499-0 |edition=15th |pages=59}}</ref> Activated macrophages in the tissue release [[cytokines]] such as [[Interleukin 1|IL-1]] and [[TNFα]], which in turn leads to production of [[chemokine]]s that bind to [[proteoglycan]]s forming gradient in the inflamed tissue and along the [[endothelial]] wall.<ref name=":2" /> Inflammatory cytokines induce the immediate expression of [[P-selectin]] on endothelial cell surfaces and P-selectin binds weakly to carbohydrate ligands on the surface of leukocytes and causes them to "roll" along the endothelial surface as bonds are made and broken. Cytokines released from injured cells induce the expression of [[E-selectin]] on endothelial cells, which functions similarly to P-selectin. Cytokines also induce the expression of [[integrin]] ligands such as [[ICAM-1]] and [[VCAM-1]] on endothelial cells, which mediate the adhesion and further slow leukocytes down. These weakly bound leukocytes are free to detach if not activated by chemokines produced in injured tissue after [[signal transduction]] via respective [[G protein-coupled receptors]] that activates integrins on the leukocyte surface for firm adhesion. Such activation increases the affinity of bound integrin receptors for ICAM-1 and VCAM-1 on the endothelial cell surface, firmly binding the leukocytes to the endothelium.
# '''Migration across the endothelium, known as'' transmigration, ''via the process of [[diapedesis]]:''' Chemokine gradients stimulate the adhered leukocytes to move between adjacent endothelial cells. The endothelial cells retract and the leukocytes pass through the basement membrane into the surrounding tissue using adhesion molecules such as ICAM-1.<ref name=":0" />
# '''Movement of leukocytes within the tissue via [[chemotaxis]]:''' Leukocytes reaching the tissue interstitium bind to [[extracellular matrix]] proteins via expressed integrins and [[CD44]] to prevent them from leaving the site. A variety of molecules behave as [[chemoattractant]]s, for example, C3a or C5a (the [[anaphylatoxins]]), and cause the leukocytes to move along a chemotactic gradient towards the source of inflammation.

=== Phagocytosis ===
{{Main|Phagocyte}}
Extravasated neutrophils in the cellular phase come into contact with microbes at the inflamed tissue. [[Phagocyte]]s express cell-surface endocytic [[pattern recognition receptors]] (PRRs) that have affinity and efficacy against non-specific [[microbe-associated molecular patterns]] (PAMPs). Most PAMPs that bind to endocytic PRRs and initiate [[phagocytosis]] are cell wall components, including complex carbohydrates such as [[mannans]] and β-[[glucans]], [[lipopolysaccharides]] (LPS), [[peptidoglycans]], and surface proteins. Endocytic PRRs on phagocytes reflect these molecular patterns, with [[C-type lectin]] receptors binding to mannans and β-glucans, and [[scavenger receptor (immunology)|scavenger receptor]]s binding to LPS.

Upon endocytic PRR binding, [[actin]]-[[myosin]] [[cytoskeletal]] rearrangement adjacent to the plasma membrane occurs in a way that [[endocytosis|endocytoses]] the plasma membrane containing the PRR-PAMP complex, and the microbe. [[Phosphatidylinositol]] and [[Vps34]]-[[PIK3R4|Vps15]]-[[BECN1|Beclin1]] signalling pathways have been implicated to traffic the endocytosed phagosome to intracellular [[lysosomes]], where fusion of the phagosome and the lysosome produces a phagolysosome. The [[reactive oxygen species]], [[superoxides]] and [[hypochlorite]] bleach within the phagolysosomes then kill microbes inside the phagocyte.

Phagocytic efficacy can be enhanced by [[opsonization]]. Plasma derived complement [[C3b]] and antibodies that exude into the inflamed tissue during the vascular phase bind to and coat the microbial antigens. As well as endocytic PRRs, phagocytes also express [[opsonin]] receptors [[Fc receptor]] and [[complement receptor 1]] (CR1), which bind to antibodies and C3b, respectively. The co-stimulation of endocytic PRR and opsonin receptor increases the efficacy of the phagocytic process, enhancing the [[lysosomal]] elimination of the infective agent.

=== Cell-derived mediators ===
{{small|''* non-exhaustive list''}}
{| class="wikitable"
!Name || Type || Source || Description
|-
| align="center" | '''[[Granule (cell biology)|Lysosome granules]]''' || align="center" | ''[[Enzyme]]s'' || align="center" | [[Granulocyte]]s || These cells contain a large variety of enzymes that perform a number of functions. Granules can be classified as either ''[[Specific granules|specific]]'' or ''[[azurophil]]ic'' depending upon the contents, and are able to break down a number of substances, some of which may be plasma-derived proteins that allow these enzymes to act as inflammatory mediators.
|-
| align="center" | '''[[Granulocyte-macrophage colony-stimulating factor|GM-CSF]]''' || align="center" | ''[[Glycoprotein]]'' || align="center" | Macrophages, monocytes, T-cells, B-cells, and tissue-resident cells || Elevated GM-CSF has been shown to contribute to inflammation in [[inflammatory arthritis]], [[osteoarthritis]], [[colitis]] [[asthma]], [[obesity]], and [[Coronavirus disease 2019|COVID-19]].
|-
| align="center" | '''[[Histamine]]''' || align="center" | ''[[Monoamine]]'' || align="center" | Mast cells and basophils || Stored in preformed granules, histamine is released in response to a number of stimuli. It causes [[arteriole]] dilation, increased [[venous]] permeability, and a wide variety of organ-specific effects.
|-
| align="center" | '''[[Interferon gamma|IFN-γ]]''' || align="center" | ''[[Cytokine]]'' || align="center" | T-cells, NK cells || Antiviral, immunoregulatory, and anti-tumour properties. This interferon was originally called macrophage-activating factor, and is especially important in the maintenance of chronic inflammation.
|-
| align="center" | '''[[Interleukin 6|IL-6]]''' || align="center" | ''[[Cytokine]]'' and ''[[Myokine]]'' || align="center" | Macrophages, osteoblasts, adipocytes, and smooth muscle cells (cytokine) Skeletal muscle cells (myokine) || Pro-inflammatory cytokine secreted by macrophages in response to [[pathogen-associated molecular pattern]]s (PAMPs); pro-inflammatory cytokine secreted by adipocytes, especially in obesity; anti-inflammatory myokine secreted by skeletal muscle cells in response to exercise.
|-
| align="center" | '''[[Interleukin 8|IL-8]]''' || align="center" | ''[[Chemokine]]'' || align="center" | Primarily [[macrophage]]s || Activation and chemoattraction of neutrophils, with a weak effect on monocytes and eosinophils.
|-
| align="center" | '''[[Leukotriene B4]]''' || align="center" | ''[[Eicosanoid]]'' || align="center" | [[Leukocytes]], cancer cells || Able to mediate leukocyte adhesion and activation, allowing them to bind to the endothelium and migrate across it. In neutrophils, it is also a potent chemoattractant, and is able to induce the formation of reactive oxygen species and the release of lysosomal enzymes by these cells.
|-
| align="center" | '''[[LTC4]]''', '''[[LTD4]]''' || align="center" | ''[[Eicosanoid]]'' || align="center" | [[eosinophils]], [[mast cells]], [[macrophages]] || These three [[Cysteine]]-containing leukotrienes contract lung airways, increase micro-vascular permeability, stimulate mucus secretion, and promote eosinophil-based inflammation in the lung, skin, nose, eye, and other tissues.
|-
| align="center" | '''[[5-oxo-eicosatetraenoic acid]]''' || align="center" | ''[[Eicosanoid]]'' || align="center" | [[Leukocytes]], cancer cells || Potent stimulator of neutrophil chemotaxis, lysosome enzyme release, and reactive oxygen species formation; monocyte chemotaxis; and with even greater potency eosinophil chemotaxis, lysosome enzyme release, and reactive oxygen species formation.
|-
| align="center" | '''[[5-HETE]]''' || align="center" | ''[[Eicosanoid]]'' || align="center" | [[Leukocytes]] || Metabolic precursor to 5-Oxo-eicosatetraenoic acid, it is a less potent stimulator of neutrophil chemotaxis, lysosome enzyme release, and reactive oxygen species formation; monocyte chemotaxis; and eosinophil chemotaxis, lysosome enzyme release, and reactive oxygen species formation.
|-
| align="center" | '''[[Prostaglandin]]s''' || align="center" | ''[[Eicosanoid]]'' || align="center" | Mast cells || A group of lipids that can cause vasodilation, fever, and pain.
|-
| align="center" | '''[[Nitric oxide]]''' || align="center" | ''Soluble gas'' || align="center" | Macrophages, endothelial cells, some neurons || Potent vasodilator, relaxes smooth muscle, reduces platelet aggregation, aids in leukocyte recruitment, direct antimicrobial activity in high concentrations.
|-
| align="center" | '''[[Tumor necrosis factor-alpha|TNF-α]] and [[Interleukin 1|IL-1]]''' || align="center" | ''[[Cytokine]]s'' || align="center" | Primarily macrophages || Both affect a wide variety of cells to induce many similar inflammatory reactions: fever, production of cytokines, endothelial gene regulation, chemotaxis, leukocyte adherence, activation of [[fibroblast]]s. Responsible for the systemic effects of inflammation, such as loss of appetite and increased heart rate. TNF-α inhibits osteoblast differentiation.
|-
| align="center" | '''[[Tryptase]]''' || align="center" | ''[[Enzyme]]s'' || align="center" | Mast Cells || This serine protease is believed to be exclusively stored in mast cells and secreted, along with histamine, during mast cell activation.<ref>{{Cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK200913/ |title=Itch: Mechanisms and Treatment |vauthors=Carstens E, Akiyama T, Cevikbas F, Kempkes C, Buhl T, Mess C, Buddenkotte J, Steinhoff M |date=2014 |publisher=CRC Press/Taylor & Francis |isbn=978-1-4665-0543-8 |veditors=Carstens M, Akiyama T |series=Frontiers in Neuroscience |location=Boca Raton (FL) |chapter=Role of Interleukin-31 and Oncostatin M in Itch and Neuroimmune Communication |pmid=24830021}}</ref><ref>{{Cite journal |vauthors=Caughey GH |date=June 2007 |title=Mast cell tryptases and chymases in inflammation and host defense |journal=Immunological Reviews |volume=217 |issue=1 |pages=141–54 |doi=10.1111/j.1600-065x.2007.00509.x |pmc=2275918 |pmid=17498057}}</ref><ref>{{Cite journal |vauthors=Caughey GH |date=May 2016 |title=Mast cell proteases as pharmacological targets |journal=European Journal of Pharmacology |series=Pharmacological modulation of Mast cells and Basophils |volume=778 |pages=44–55 |doi=10.1016/j.ejphar.2015.04.045 |pmc=4636979 |pmid=25958181}}</ref>
|}