Editing Inflammation (section)

=== 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.