Editing Platelet (section)

==Immune function==
Platelets have a central role in [[innate immunity]], initiating and participating in multiple inflammatory processes, directly binding and even destroying pathogens. Clinical data show that many patients with serious bacterial or viral infections have [[thrombocytopenia]], thus reducing their contribution to inflammation. Platelet-leukocyte aggregates (PLAs) found in circulation are typical in [[sepsis]] or [[inflammatory bowel disease]], showing the connection between thrombocytes and immune cells.<ref name=":1">{{cite journal |vauthors=Jenne CN, Urrutia R, Kubes P |title=Platelets: bridging hemostasis, inflammation, and immunity |journal=International Journal of Laboratory Hematology |volume=35 |issue=3 |pages=254–261 |date=June 2013 |pmid=23590652 |doi=10.1111/ijlh.12084 |doi-access=free}}</ref>

The platelet cell membrane has receptors for collagen. Following rupture of the blood vessel wall, platelets are exposed and adhere to the collagen in the surrounding tissue.

===Immunothrombosis===
As hemostasis is a basic function of thrombocytes in mammals, it also has its uses in possible infection confinement.<ref name=":0"/> In case of injury, platelets, together with the coagulation cascade, provide the first line of defense by forming a blood clot. Hemostasis and host defense were thus intertwined in evolution. For example, in the [[Atlantic horseshoe crab]] (estimated to be over 400&nbsp;million years old), the only blood cell type, the [[amebocyte]], facilitates both the hemostatic function and immune functions, including encapsulation, phagocytosis of [[pathogen]]s, and [[exocytosis]] of intracellular granules containing [[bactericide|bactericidal]] defense molecules. Blood clotting supports immune function by trapping the bacteria.<ref>{{citation |last=Levin |first=Jack |name-list-style=vanc |title=Platelets |chapter=The Evolution of Mammalian Platelets |date=2007 |pages=3–22 |publisher=Elsevier |isbn=978-0-12-369367-9 |doi=10.1016/B978-012369367-9/50763-1 }}</ref>

Thrombosis (blood coagulation in intact blood vessels) is usually viewed as a pathological immune response, leading to obturation of lumen of blood vessel and subsequent hypoxic tissue damage. In some cases, however, directed thrombosis (or ''immunothrombosis)'' can locally control the spread of an infection. The thrombosis is directed in concordance with platelets, [[neutrophil]]s and [[monocyte]]s. The process is initiated either by immune cells by activating their pattern recognition receptors (PRRs), or by platelet-bacterial binding. Platelets can bind to bacteria either directly through thrombocytic PRRs<ref name=":1"/> and bacterial surface proteins, or via plasma proteins that bind both to platelets and bacteria.<ref>{{cite journal |vauthors=Cox D, Kerrigan SW, Watson SP |title=Platelets and the innate immune system: mechanisms of bacterial-induced platelet activation |journal=Journal of Thrombosis and Haemostasis |volume=9 |issue=6 |pages=1097–1107 |date=June 2011 |pmid=21435167 |doi=10.1111/j.1538-7836.2011.04264.x |url=https://epubs.rcsi.ie/cgi/viewcontent.cgi?article=1041&context=mctart |doi-access=free}}</ref> Monocytes respond to bacterial [[pathogen-associated molecular pattern]]s (PAMPs), or [[damage-associated molecular pattern]]s (DAMPs) by activating the extrinsic pathway of coagulation. Neutrophils facilitate the blood coagulation by [[Neutrophil extracellular traps|NETosis]], while platelets facilitate neutrophils' NETosis. NETs bind tissue factor, binding the coagulation centers to the location of infection. They also activate the intrinsic coagulation pathway by providing a negatively charged surface for factor XII. Other neutrophil secretions, such as proteolytic enzymes which cleave coagulation inhibitors, also bolster the process.<ref name=":0"/>

In case of imbalance in the regulation of immunothrombosis, this process can become aberrant. Regulatory defects in immunothrombosis are suspected to be a major factor in pathological thrombosis in forms such as [[disseminated intravascular coagulation]] (DIC) or [[deep vein thrombosis]]. DIC in sepsis is a prime example of both the dysregulated coagulation process and an undue systemic inflammatory response. It results in a multitude of microthrombi. These are similar in composition to the thrombi produced in native immunothrombosis — they are made up of fibrin, platelets, neutrophils and NETs.<ref name=":0"/>

===Inflammation===
Platelets rapidly deploy to sites of injury or infection. There, they are thought to modulate inflammatory processes ''via'' interactions with [[leukocyte]]s and secretion of [[cytokine]]s, [[chemokine]]s, and other inflammatory mediators.<ref>{{cite journal |vauthors=Weyrich AS, Zimmerman GA |title=Platelets: signaling cells in the immune continuum |journal=Trends in Immunology |volume=25 |issue=9 |pages=489–495 |date=September 2004 |pmid=15324742 |doi=10.1016/j.it.2004.07.003}}</ref><ref name="pmid14500287">{{cite journal |vauthors=Wagner DD, Burger PC |title=Platelets in inflammation and thrombosis |journal=Arteriosclerosis, Thrombosis, and Vascular Biology |volume=23 |issue=12 |pages=2131–7 |date=December 2003 |pmid=14500287 |doi=10.1161/01.ATV.0000095974.95122.EC |doi-access=free}}</ref><ref name="pmid8662511">{{cite journal |vauthors=Diacovo TG, Puri KD, Warnock RA, Springer TA, von Andrian UH |title=Platelet-mediated lymphocyte delivery to high endothelial venules |journal=Science |volume=273 |issue=5272 |pages=252–5 |date=July 1996 |pmid=8662511 |doi=10.1126/science.273.5272.252 |bibcode=1996Sci...273..252D |s2cid=21334521}}</ref><ref name="pmid16258538">{{cite journal |vauthors=Iannacone M, Sitia G, Isogawa M, Marchese P, Castro MG, Lowenstein PR, Chisari FV, Ruggeri ZM, Guidotti LG |title=Platelets mediate cytotoxic T lymphocyte-induced liver damage |journal=Nature Medicine |volume=11 |issue=11 |pages=1167–9 |date=November 2005 |pmid=16258538 |pmc=2908083 |doi=10.1038/nm1317}}</ref><ref>{{cite journal |last1=Oehlers |first1=Stefan H. |last2=Tobin |first2=David M. |last3=Britton |first3=Warwick J. |last4=Shavit |first4=Jordan A. |last5=Nguyen |first5=Tuong |last6=Johansen |first6=Matt D. |last7=Johnson |first7=Khelsey E. |last8=Hortle |first8=Elinor |title=Thrombocyte inhibition restores protective immunity to mycobacterial infection in zebrafish |url= |journal=The Journal of Infectious Diseases |volume=220 |issue=3 |pages=524–534 |language=en |doi=10.1093/infdis/jiz110 |pmid=30877311 |pmc=6603966 |year=2019}}</ref> Platelets also secrete [[platelet-derived growth factor]] (PDGF).

Platelets modulate neutrophils by forming platelet-leukocyte aggregates (PLAs). These formations induce upregulated production of the [[complement receptor]] αmβ2 ([[integrin alpha M|Mac-1]]) integrin in neutrophils. Interaction with PLAs also induces degranulation and increased phagocytosis in neutrophils.

Platelets are the largest source of soluble [[CD40L|CD40L (CD154)]] which induces production of [[reactive oxygen species]] (ROS) and upregulates expression of adhesion molecules (such as [[E-selectin]], [[ICAM-1]], and [[VCAM-1]]) in neutrophils. CD40L also activates macrophages and activates cytotoxic response in [[T lymphocyte|T]] and [[B lymphocytes]].<ref name=":1" />

Mammalian platelets lacking nucleus are able to conduct autonomous locomotion.<ref>{{cite journal |vauthors=Gaertner F, Ahmad Z, Rosenberger G, Fan S, Nicolai L, Busch B, Yavuz G, Luckner M, Ishikawa-Ankerhold H, Hennel R, Benechet A, Lorenz M, Chandraratne S, Schubert I, Helmer S, Striednig B, Stark K, Janko M, Böttcher RT, Verschoor A, Leon C, Gachet C, Gudermann T, Mederos Y, Schnitzler M, Pincus Z, Iannacone M, Haas R, Wanner G, Lauber K, Sixt M, Massberg S |title=Migrating Platelets Are Mechano-scavengers that Collect and Bundle Bacteria |journal=Cell |volume=171 |issue=6 |pages=1368–82 |date=November 2017 |pmid=29195076 |doi=10.1016/j.cell.2017.11.001 |doi-access=free}}</ref> Platelets are active scavengers, scaling walls of blood vessels and reorganising the thrombus. They are able to recognize and adhere to many surfaces, including bacteria, and can envelop them in their open canalicular system (OCP), leading to a proposal to name the process as ''covercytosis'' (OCS) rather than phagocytosis, as OCS is merely an invagination of outer plasma membrane. These platelet-bacteria bundles provide an interaction platform for neutrophils that destroy bacteria using [[Neutrophil extracellular traps|NETs]] and phagocytosis.

Platelets also participate in chronic inflammatory disease, such as [[synovitis]] or [[rheumatoid arthritis]].<ref>{{cite journal |vauthors=Boilard E, Nigrovic PA, Larabee K, Watts GF, Coblyn JS, Weinblatt ME, Massarotti EM, Remold-O'Donnell E, Farndale RW, Ware J, Lee DM |title=Platelets amplify inflammation in arthritis via collagen-dependent microparticle production |journal=Science |volume=327 |issue=5965 |pages=580–3 |date=January 2010 |pmid=20110505 |pmc=2927861 |doi=10.1126/science.1181928 |bibcode=2010Sci...327..580B}}</ref> Platelets are activated by collagen receptor [[GPVI|glycoprotein IV]] (GPVI). Proinflammatory platelet microvesicles trigger constant cytokine secretion from neighboring [[fibroblast-like synoviocyte]]s, most prominently [[interleukin 6|Il-6]] and [[interleukin 8|Il-8]]. Inflammatory damage to the surrounding extracellular matrix continuously reveals more collagen, binding receptors on platelets and maintaining microvesicle production.

===Adaptive immunity===
Activated platelets are able to participate in [[adaptive immunity]], interacting with [[antibody|antibodies]]. They are able to specifically bind [[immunoglobulin G|IgG]] through [[FcγRIIA]], a receptor for IgG's constant fragment (Fc). When activated and bound to IgG-[[opsonin|opsonised]] bacteria, platelets release reactive oxygen species (ROS), antimicrobial peptides, [[defensins]], kinocidins and [[proteases]], killing the bacteria directly.<ref name=":2">{{cite journal |vauthors=Palankar R, Kohler TP, Krauel K, Wesche J, Hammerschmidt S, Greinacher A |title=Platelets kill bacteria by bridging innate and adaptive immunity via platelet factor 4 and FcγRIIA |journal=Journal of Thrombosis and Haemostasis |volume=16 |issue=6 |pages=1187–97 |date=June 2018 |pmid=29350833 |doi=10.1111/jth.13955 |doi-access=free}}</ref> Platelets also secrete proinflammatory and procoagulant mediators such as inorganic [[polyphosphates]] or [[platelet factor 4]] (PF4), connecting innate and adaptive immune responses.<ref name=":2"/><ref>{{cite journal |vauthors=McMorran BJ, Wieczorski L, Drysdale KE, Chan JA, Huang HM, Smith C, Mitiku C, Beeson JG, Burgio G, Foote SJ |title=Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum |journal=Science |volume=338 |issue=6112 |pages=1348–51 |date=December 2012 |pmid=23224555 |doi=10.1126/science.1228892 |bibcode=2012Sci...338.1348M |s2cid=206544569 |url=https://zenodo.org/record/261563}}</ref>