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===Chemotactic ligands=== [[Image:chtxChemokineStruct.png|right|350 px|<div style="text-align: center;border:none">Structure of chemokine classes</div>]] [[Image:chtxChemkinStr2.png|left|300 px|<div style="text-align: center;border:none">Three dimensional structure of chemokines</div>]] The number of molecules capable of eliciting chemotactic responses is relatively high, and we can distinguish primary and secondary chemotactic molecules.{{citation needed|date=March 2017}} The main groups of the primary ligands are as follows: * ''Formyl peptides'' are di-, tri-, tetrapeptides of bacterial origin, formylated on the N-terminus of the peptide.{{citation needed|date=March 2017}}<ref>{{cite journal | vauthors = Zigmond SH | title = Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors | journal = The Journal of Cell Biology | volume = 75 | issue = 2 Pt 1 | pages = 606–16 | date = November 1977 | pmid = 264125 | pmc = 2109936 | doi = 10.1083/jcb.75.2.606 }}</ref> They are released from bacteria in vivo or after decomposition of the cell, a typical member of this group is the N-formylmethionyl-leucyl-phenylalanine (abbreviated fMLF or fMLP).{{citation needed|date=March 2017}} Bacterial fMLF is a key component of inflammation has characteristic chemoattractant effects in neutrophil granulocytes and monocytes.{{citation needed|date=March 2017}} The chemotactic factor ligands and receptors related to formyl peptides are summarized in the related article, [[Formyl peptide receptors]]. * ''Complement 3a ([[C3 (complement)|C3a]]) and complement 5a ([[Complement component 5a|C5a]])'' are intermediate products of the complement cascade.{{citation needed|date=March 2017}} Their synthesis is joined to the three alternative pathways (classical, lectin-dependent, and alternative) of complement activation by a convertase enzyme.{{citation needed|date=March 2017}} The main target cells of these derivatives are neutrophil granulocytes and monocytes as well.{{citation needed|date=March 2017}} * ''[[Chemokines]]'' belong to a special class of [[cytokines]]; not only do their groups (C, CC, CXC, CX<sub>3</sub>C chemokines) represent structurally related molecules with a special arrangement of disulfide bridges but also their target cell specificity is diverse.{{citation needed|date=March 2017}} CC chemokines act on monocytes (e.g., [[RANTES]]), and CXC chemokines are neutrophil granulocyte-specific (e.g., [[Interleukin 8|IL-8]]).{{citation needed|date=March 2017}} Investigations of the three-dimensional structures of chemokines provided evidence that a characteristic composition of beta-sheets and an alpha helix provides expression of sequences required for interaction with the chemokine receptors.{{citation needed|date=March 2017}} Formation of dimers and their increased biological activity was demonstrated by crystallography of several chemokines, e.g. IL-8.{{citation needed|date=March 2017}} *Metabolites of [[polyunsaturated fatty acid]]s ** ''[[Leukotrienes]]'' are [[eicosanoid]] lipid mediators made by the metabolism of [[arachidonic acid]] by [[ALOX5]] (also termed 5-lipoxygenase). Their most prominent member with chemotactic factor activity is [[leukotriene B4]], which elicits adhesion, chemotaxis, and aggregation of leukocytes. The chemoattractant action of LTB4 is induced via either of two [[G protein–coupled receptor]]s, BLT1 and [[BLT2]], which are highly expressed in cells involved in [[inflammation]] and [[allergy]].<ref name="pmid25449650">{{cite journal | vauthors = Powell WS, Rokach J | title = Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1851 | issue = 4 | pages = 340–55 | date = April 2015 | pmid = 25449650 | pmc = 5710736 | doi = 10.1016/j.bbalip.2014.10.008 }}</ref> ** The family of [[5-Hydroxyicosatetraenoic acid]] eicosanoids are arachidonic acid metabolites also formed by ALOX5. Three members of the family form naturally and have prominent chemotactic activity. These, listed in order of decreasing potency, are: ''[[5-oxo-eicosatetraenoic acid]]'', ''5-oxo-15-hydroxy-eicosatetraenoic acid'', and ''[[5-Hydroxyeicosatetraenoic acid]]''. This family of agonists stimulates chemotactic responses in human [[eosinophils]], [[neutrophils]], and [[monocytes]] by binding to the [[Oxoeicosanoid receptor 1]], which like the receptors for leukotriene B4, is a G protein-coupled receptor.<ref name="pmid25449650"/> Aside from the skin, [[neutrophils]] are the body's first line of defense against [[bacterial]] infections. After leaving nearby blood vessels, these cells recognize chemicals produced by bacteria in a cut or scratch and migrate "toward the smell". **''5-hydroxyeicosatrienoic acid'' and ''5-oxoeicosatrienoic acid'' are metabolites of [[Mead acid]] (5''Z'',8''Z'',11''Z''-eicosatrirenoid acid); they stimulate leukocyte chemotaxis through the oxoeicosanoid receptor 1<ref name="pmid24056189">{{cite journal | vauthors = Powell WS, Rokach J | title = The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor | journal = Progress in Lipid Research | volume = 52 | issue = 4 | pages = 651–65 | date = October 2013 | pmid = 24056189 | pmc = 5710732 | doi = 10.1016/j.plipres.2013.09.001 }}</ref> with 5-oxoeicosatrienoic acid being as potent as its arachidonic acid-derived analog, 5-oxo-eicosatetraenoic acid, in stimulating human blood [[eosinophil]] and [[neutrophil]] chemotaxis.<ref name="pmid25449650"/> **''[[12-Hydroxyeicosatetraenoic acid]]'' is an eicosanoid metabolite of arachidonic acid made by [[ALOX12]] which stimulates leukocyte chemotaxis through the leukotriene B4 receptor, BLT2.<ref name="pmid25449650"/> **''[[Prostaglandin D2]]'' is an eicosanoid metabolite of arachidononic acid made by [[cyclooxygenase 1]] or [[cyclooxygenase 2]] that stimulates chemotaxis through the [[Prostaglandin DP2 receptor]]. It elicits chemotactic responses in eosinophils, basophils, and [[T helper cell]]s of the Th2 subtype.<ref name="pmid17767353">{{cite journal | vauthors = Matsuoka T, Narumiya S | title = Prostaglandin receptor signaling in disease | journal = TheScientificWorldJournal | volume = 7 | pages = 1329–47 | date = September 2007 | pmid = 17767353 | pmc = 5901339 | doi = 10.1100/tsw.2007.182 | doi-access = free }}</ref>{{primary source inline|date=March 2017}}{{primary source inline|date=March 2017}} **''[[12-Hydroxyheptadecatrienoic acid]]'' is a non-eicosanoid metabolite of arachidonic acid made by cyclooxygenase 1 or cyclooxygenase 2 that stimulates leukocyte chemotaxis though the leukotriene B4 receptor, BLT2.<ref name="pmid25480980">{{cite journal | vauthors = Yokomizo T | title = Two distinct leukotriene B4 receptors, BLT1 and BLT2 | journal = Journal of Biochemistry | volume = 157 | issue = 2 | pages = 65–71 | date = February 2015 | pmid = 25480980 | doi = 10.1093/jb/mvu078 | doi-access = }}</ref>{{primary source inline|date=March 2017}}{{primary source inline|date=March 2017}} **''15-oxo-eicosatetraenoic acid'' is an eicosanoid metabolite of arachidonic acid made my [[ALOX15]]; it has weak chemotactic activity for human monocytes (sees [[15-Hydroxyeicosatetraenoic acid#15-oxo-ETE]]).<ref>{{cite journal | vauthors = Sozzani S, Zhou D, Locati M, Bernasconi S, Luini W, Mantovani A, O'Flaherty JT | title = Stimulating properties of 5-oxo-eicosanoids for human monocytes: synergism with monocyte chemotactic protein-1 and -3 | journal = Journal of Immunology | volume = 157 | issue = 10 | pages = 4664–71 | date = November 1996 | doi = 10.4049/jimmunol.157.10.4664 | pmid = 8906847 | s2cid = 23499393 | doi-access = free }}</ref>{{primary source inline|date=March 2017}}{{primary source inline|date=March 2017}} The receptor or other mechanism by which this metabolite stimulates chemotaxis has not been elucidated. ==== Chemotactic range fitting ==== [[File:chtxCRF2.png|right|thumb|alt=Chemotactic range fitting|[[Chemotactic range fitting]]]] Chemotactic responses elicited by [[ligand (biochemistry)|ligand]]-[[receptor (biochemistry)|receptor]] interactions vary with the concentration of the ligand. Investigations of ligand families (e.g. [[amino acids]] or [[oligopeptide]]s) demonstrates that [[chemoattractant]] activity occurs over a wide range, while [[chemorepellent]] activities have narrow ranges.<ref>{{cite journal | author=Kohidai L, Lang O and Csaba G | title=Chemotactic-range-fitting of amino acids and its correlations to physicochemical parameters in Tetrahymena pyriformis - Evolutionary consequences | journal= Cellular and Molecular Biology | year=2003 | volume=49 | pages=OL487–95 | pmid=14995080}}</ref>
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