Editing Inflammation (section)

== Vascular component ==
{{More medical citations needed|section|date=March 2021}}

=== Vasodilation and increased permeability ===

As defined, acute inflammation is an immunovascular response to inflammatory stimuli, which can include infection or trauma.<ref name=":1">{{Cite journal |vauthors=Raiten DJ, Sakr Ashour FA, Ross AC, Meydani SN, Dawson HD, Stephensen CB, Brabin BJ, Suchdev PS, van Ommen B |date=May 2015 |title=Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE) |journal=The Journal of Nutrition |volume=145 |issue=5 |pages=1039S–1108S |doi=10.3945/jn.114.194571 |pmc=4448820 |pmid=25833893}}</ref><ref>{{Cite journal |vauthors=Taams LS |date=July 2018 |title=Inflammation and immune resolution |journal=Clinical and Experimental Immunology |volume=193 |issue=1 |pages=1–2 |doi=10.1111/cei.13155 |pmc=6037995 |pmid=29987840}}</ref> This means acute inflammation can be broadly divided into a vascular phase that occurs first, followed by a cellular phase involving immune cells (more specifically myeloid [[granulocytes]] in the acute setting).<ref name=":1" /> The vascular component of acute inflammation involves the movement of [[Blood plasma|plasma fluid]], containing important [[protein]]s such as [[fibrin]] and [[immunoglobulin]]s ([[antibodies]]), into inflamed tissue.

Upon contact with PAMPs, tissue [[macrophages]] and [[mastocytes]] release vasoactive amines such as [[histamine]] and [[serotonin]], as well as [[eicosanoids]] such as [[prostaglandin E2]] and [[leukotriene B4]] to remodel the local vasculature.<ref name=":2">{{Cite journal |vauthors=Medzhitov R |date=July 2008 |title=Origin and physiological roles of inflammation |journal=Nature |volume=454 |issue=7203 |pages=428–435 |bibcode=2008Natur.454..428M |doi=10.1038/nature07201 |pmid=18650913 |s2cid=205214291}}</ref> Macrophages and endothelial cells release [[nitric oxide]].<ref>{{Cite journal |vauthors=Mantovani A, Garlanda C |date=February 2023 |title=Humoral Innate Immunity and Acute-Phase Proteins |journal=The New England Journal of Medicine |volume=388 |issue=5 |pages=439–452 |doi=10.1056/NEJMra2206346 |pmc=9912245 |pmid=36724330 |veditors=Longo DL}}</ref> These mediators vasodilate and permeabilize the [[blood vessel]]s, which results in the net distribution of [[blood plasma]] from the vessel into the tissue space. The increased collection of fluid into the tissue causes it to swell ([[edema]]).<ref name=":2" /> This exuded tissue fluid contains various antimicrobial mediators from the plasma such as [[complement system|complement]], [[lysozyme]], [[antibodies]], which can immediately deal damage to microbes, and [[Opsonin|opsonise]] the microbes in preparation for the cellular phase. If the inflammatory stimulus is a lacerating wound, exuded [[platelet]]s, [[coagulation system|coagulant]]s, [[plasmin]] and [[kinin]]s can [[clot]] the wounded area using vitamin K-dependent mechanisms<ref>{{cite book | vauthors = Ferland G | chapter = Vitamin K |date=2020 | title = Present Knowledge in Nutrition |pages=137–153 | chapter-url = https://linkinghub.elsevier.com/retrieve/pii/B9780323661621000081 |access-date=2023-02-17 |publisher=Elsevier |language=en |doi=10.1016/b978-0-323-66162-1.00008-1 |isbn=978-0-323-66162-1}}</ref> and provide [[haemostasis]] in the first instance. These clotting mediators also provide a structural staging framework at the inflammatory tissue site in the form of a [[fibrin]] lattice – as would construction [[scaffolding]] at a construction site – for the purpose of aiding phagocytic debridement and [[wound healing|wound repair]] later on. Some of the exuded tissue fluid is also funneled by [[lymphatics]] to the regional lymph nodes, flushing bacteria along to start the recognition and attack phase of the [[adaptive immune system]].

[[File:Toe.JPG|thumb|right|230px|Infected [[ingrown toenail]] showing the characteristic redness and swelling associated with acute inflammation]]

Acute inflammation is characterized by marked vascular changes, including [[vasodilation]], increased permeability and increased blood flow, which are induced by the actions of various inflammatory mediators.<ref name=":2" /> Vasodilation occurs first at the [[arteriole]] level, progressing to the [[capillary]] level, and brings about a net increase in the amount of blood present, causing the redness and heat of inflammation. Increased permeability of the vessels results in the movement of [[blood plasma|plasma]] into the tissues, with resultant [[Venous stasis|stasis]] due to the increase in the concentration of the cells within blood – a condition characterized by enlarged vessels packed with cells. Stasis allows [[leukocytes]] to marginate (move) along the [[endothelium]], a process critical to their recruitment into the tissues. Normal flowing blood prevents this, as the [[Shear stress|shearing force]] along the periphery of the vessels moves cells in the blood into the middle of the vessel.

=== Plasma cascade systems ===
* The [[complement system]], when activated, creates a cascade of chemical reactions that promotes [[Antibody opsonization|opsonization]], [[chemotaxis]], and [[agglutination (biology)|agglutination]], and produces the [[Membrane attack complex|MAC]].
* The [[kinin system]] generates proteins capable of sustaining vasodilation and other physical inflammatory effects.
* The [[coagulation system]] or ''clotting cascade'', which forms a protective protein mesh over sites of injury.
* The [[fibrinolysis system]], which acts in opposition to the ''coagulation system'', to counterbalance clotting and generate several other inflammatory mediators.

=== Plasma-derived mediators ===
{{small|''* non-exhaustive list''}}
{| class="wikitable"
! Name || Produced by || Description
|-
| align="center" | '''[[Bradykinin]]''' || align="center" | ''[[Kinin system]]'' || A vasoactive protein that is able to induce vasodilation, increase vascular permeability, cause smooth muscle contraction, and induce pain.
|-
| align="center" | '''[[C3 (complement)|C3]]''' || align="center" | ''[[Complement system]]'' || Cleaves to produce ''C3a'' and ''C3b''. C3a stimulates histamine release by mast cells, thereby producing vasodilation. C3b is able to bind to bacterial cell walls and act as an [[opsonin]], which marks the invader as a target for [[phagocytosis]].
|-
| align="center" | '''[[Complement component 5a|C5a]]'''  || align="center" | ''[[Complement system]]'' || Stimulates histamine release by mast cells, thereby producing vasodilation. It is also able to act as a [[chemoattractant]] to direct cells via chemotaxis to the site of inflammation.
|-
| align="center" | '''[[Factor XII]]''' (''Hageman Factor'') || align="center" | ''[[Liver]]'' || A protein that circulates inactively, until activated by collagen, platelets, or exposed [[basement membrane]]s via [[conformational change]]. When activated, it in turn is able to activate three plasma systems involved in inflammation: the kinin system, fibrinolysis system, and coagulation system.
|-
| align="center" | '''[[Membrane attack complex]]''' || align="center" | ''[[Complement system]]'' || A complex of the complement proteins [[C5b]], [[Complement component 6|C6]], [[Complement component 7|C7]], [[C8 complex|C8]], and multiple units of [[Complement component 9|C9]]. The combination and activation of this range of complement proteins forms the ''membrane attack complex'', which is able to insert into bacterial cell walls and causes cell lysis with ensuing bacterial death.
|-
| align="center" | '''[[Plasmin]]''' || align="center" | ''[[Fibrinolysis system]]'' || Able to break down fibrin clots, cleave complement protein C3, and activate Factor XII.
|-
| align="center" | '''[[Thrombin]]''' || align="center" | ''[[Coagulation system]]'' || Cleaves the soluble plasma protein [[fibrinogen]] to produce insoluble [[fibrin]], which aggregates to form a [[blood clot]]. Thrombin can also bind to cells via the [[Protease-activated receptor|PAR1]] receptor to trigger several other inflammatory responses, such as production of [[chemokine]]s and [[nitric oxide]].
|}