Editing Chemotaxis (section)

==Eukaryotic chemotaxis==
[[Image:Chtxbaceukkl1.png|right|350 px|<div style="text-align: center;border:none">Difference of gradient sensing in prokaryotes and eukaryotes</div>]]
The mechanism of chemotaxis that [[eukaryotic]] cells employ is quite different from that in the bacteria ''E. coli''; however, sensing of chemical gradients is still a crucial step in the process.<ref>{{cite book | vauthors = Köhidai L |chapter=Chemotaxis as an Expression of Communication of Tetrahymena|title=Biocommunication of Ciliates| veditors = Witzany G, Nowacki M |date=2016|pages=65&ndash;82|doi=10.1007/978-3-319-32211-7_5|isbn=978-3-319-32211-7}}</ref>{{better source needed|date=March 2017}} Due to their small size and other biophysical constraints, ''E. coli'' cannot directly detect a concentration gradient.<ref>{{cite journal | vauthors = Berg HC, Purcell EM | title = Physics of chemoreception | journal = Biophysical Journal | volume = 20 | issue = 2 | pages = 193–219 | date = November 1977 | pmid = 911982 | pmc = 1473391 | doi = 10.1016/s0006-3495(77)85544-6 | bibcode = 1977BpJ....20..193B }}</ref> Instead, they employ temporal gradient sensing, where they move over larger distances several times their own width and measure the rate at which perceived chemical concentration changes.<ref name="Levine2013">{{cite journal | vauthors = Levine H, Rappel WJ | title = The physics of eukaryotic chemotaxis | journal = Physics Today | volume = 66 | issue = 2 | pages = 24–30 | date = February 2013 | pmid = 24363460 | pmc = 3867297 | doi = 10.1063/PT.3.1884 | bibcode = 2013PhT....66b..24L }}</ref><ref name="Vlad2009">{{cite journal | vauthors = Vladimirov N, Sourjik V | title = Chemotaxis: how bacteria use memory | journal = Biological Chemistry | volume = 390 | issue = 11 | pages = 1097–1104 | date = November 2009 | pmid = 19747082 | doi = 10.1515/BC.2009.130 | s2cid = 207440927 }}</ref>

Eukaryotic cells are much larger than prokaryotes and have receptors embedded uniformly throughout the [[cell membrane]].<ref name="Levine2013" /> Eukaryotic chemotaxis involves detecting a concentration gradient spatially by comparing the asymmetric activation of these receptors at the different ends of the cell.<ref name="Levine2013" /> Activation of these receptors results in migration towards chemoattractants, or away from chemorepellants.<ref name="Levine2013" /> In mating yeast, which are non-motile, patches of polarity proteins on the cell cortex can relocate in a chemotactic fashion up pheromone gradients.<ref>{{cite journal | vauthors = Ghose D, Lew D | title = Mechanistic insights into actin-driven polarity site movement in yeast | journal = Molecular Biology of the Cell | volume = 31 | issue = 10 | pages = 1085–1102 | date = May 2020 | pmid = 32186970 | pmc = 7346724 | doi = 10.1091/mbc.e20-01-0040 }}</ref><ref name="Ghose"/>

It has also been shown that both prokaryotic and eukaryotic cells are capable of chemotactic memory.<ref name="Vlad2009" /><ref name="Skoge2014">{{cite journal | vauthors = Skoge M, Yue H, Erickstad M, Bae A, Levine H, Groisman A, Loomis WF, Rappel WJ | title = Cellular memory in eukaryotic chemotaxis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 40 | pages = 14448–53 | date = October 2014 | pmid = 25249632 | pmc = 4210025 | doi = 10.1073/pnas.1412197111 | bibcode = 2014PNAS..11114448S | doi-access = free }}</ref> In prokaryotes, this mechanism involves the [[methylation]] of receptors called [[methyl-accepting chemotaxis protein]]s (MCPs).<ref name="Vlad2009" /> This results in their desensitization and allows prokaryotes to "remember" and adapt to a chemical gradient.<ref name="Vlad2009" /> In contrast, chemotactic memory in eukaryotes can be explained by the Local Excitation Global Inhibition (LEGI) model.<ref name="Skoge2014"/><ref name="Kutscher2004">{{cite journal | vauthors = Kutscher B, Devreotes P, Iglesias PA | title = Local excitation, global inhibition mechanism for gradient sensing: an interactive applet | journal = Science's STKE | date = Feb 2004 | volume = 2004 | issue = 219 | pages = pl3 | pmid = 14872096 | doi = 10.1126/stke.2192004pl3 | s2cid = 4660870 }}</ref> LEGI involves the balance between a fast excitation and delayed inhibition which controls downstream signaling such as [[Ras subfamily|Ras]] activation and [[Phosphatidylinositol (3,4,5)-trisphosphate|PIP3]] production.<ref>{{cite journal | vauthors = Xiong Y, Huang CH, Iglesias PA, Devreotes PN | title = Cells navigate with a local-excitation, global-inhibition-biased excitable network | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 40 | pages = 17079–86 | date = October 2010 | pmid = 20864631 | pmc = 2951443 | doi = 10.1073/pnas.1011271107 | bibcode = 2010PNAS..10717079X | doi-access = free }}</ref>

Levels of receptors, intracellular signalling pathways and the effector mechanisms all represent diverse, eukaryotic-type components. In eukaryotic unicellular cells, amoeboid movement and cilium or the eukaryotic flagellum are the main effectors (e.g., [[Amoeba (genus)|Amoeba]] or [[Tetrahymena]]).<ref>{{cite journal | vauthors = Bagorda A, Parent CA | title = Eukaryotic chemotaxis at a glance | journal = Journal of Cell Science | volume = 121 | issue = Pt 16 | pages = 2621–4 | date = August 2008 | pmid = 18685153 | doi = 10.1242/jcs.018077 | pmc = 7213762 | citeseerx = 10.1.1.515.32 }}</ref><ref>{{cite journal | vauthors = Köhidai L | title = Chemotaxis: the proper physiological response to evaluate phylogeny of signal molecules | journal = Acta Biologica Hungarica | volume = 50 | issue = 4 | pages = 375–94 | year = 1999 | doi = 10.1007/BF03543060 | pmid = 10735174 | s2cid = 248703226 }}</ref> Some eukaryotic cells of [[higher vertebrate]] origin, such as [[immune system|immune cells]] also move to where they need to be. Besides immune competent cells ([[granulocyte]], [[monocyte]], [[lymphocyte]]) a large group of cells—considered previously to be fixed into tissues—are also motile in special physiological (e.g., [[mast cell]], [[fibroblast]], [[endothelial cells]]) or pathological conditions (e.g., [[metastases]]).<ref>{{cite journal | vauthors = Kedrin D, van Rheenen J, Hernandez L, Condeelis J, Segall JE | s2cid = 31704677 | title = Cell motility and cytoskeletal regulation in invasion and metastasis | journal = Journal of Mammary Gland Biology and Neoplasia | volume = 12 | issue = 2–3 | pages = 143–52 | date = September 2007 | pmid = 17557195 | doi = 10.1007/s10911-007-9046-4 }}</ref> Chemotaxis has high significance in the early phases of [[embryogenesis]] as development of [[germ layers]] is guided by gradients of signal molecules.<ref>{{cite journal | vauthors = Solnica-Krezel L, Sepich DS | s2cid = 11331182 | title = Gastrulation: making and shaping germ layers | journal = Annual Review of Cell and Developmental Biology | volume = 28 | pages = 687–717 | date = 2012 | pmid = 22804578 | doi = 10.1146/annurev-cellbio-092910-154043 }}</ref><ref>{{cite journal | vauthors = Shellard A, Mayor R | title = Chemotaxis during neural crest migration | journal = Seminars in Cell & Developmental Biology | volume = 55 | pages = 111–8 | date = July 2016 | pmid = 26820523 | doi = 10.1016/j.semcdb.2016.01.031 }}</ref>

===Detection of a gradient of chemoattractant===
The specific molecule/s that allow a eukaryotic cells detect a gradient of chemoattractant ligands (that is, a sort of the molecular compass that detects the direction of a chemoattractant) seems to change depending on the cell and chemoattractant receptor involved or even the concentration of the chemoattractant. However, these molecules apparently are activated independently of the motility of the cell. That is, even an immnobilized cell is still able to detect the direction of a chemoattractant.<ref>{{cite journal | vauthors = Rodríguez-Fernández JL, Criado-García O | title = A meta-analysis indicates that the regulation of cell motility is a non-intrinsic function of chemoattractant receptors that is governed independently of directional sensing | journal = Front. Immunol. | volume = 13 | issue = eCollection 2022 | pages = 10011086 | date = October 2022 | pmid = 36341452}}</ref> There appear to be mechanisms by which an external chemotactic gradient is sensed and turned into an intracellular Ras and [[PIP3]] gradients, which results in a gradient and the activation of a signaling pathway, culminating in the [[polymerisation]] of [[actin]] filaments. The growing distal end of actin filaments develops connections with the internal surface of the plasma membrane via different sets of peptides and results in the formation of anterior [[pseudopods]] and posterior [[Uropod (immunology)|uropods]].<ref>{{cite journal | vauthors = Pal DS, Banerjee T, Lin Y, de Trogoff F, Borleis J, Iglesias PA, Devreotes PN | title = Actuation of single downstream nodes in growth factor network steers immune cell migration | journal = Developmental Cell | volume = 58 | issue = 13 | pages = 1170–1188.e7 | date = July 2023 | pmid = 37220748 | pmc = 10524337 | doi = 10.1016/j.devcel.2023.04.019 }}</ref><ref>{{cite journal | vauthors = Lin Y, Pal DS, Banerjee P, Banerjee T, Qin G, Deng Y, Borleis J, Iglesias PA, Devreotes PN | title = Ras suppression potentiates rear actomyosin contractility-driven cell polarization and migration | journal = Nature Cell Biology | pages = 1–15 | date = July 2024 | pmid = 38951708 | doi = 10.1038/s41556-024-01453-4 | pmc = 11364469 }}</ref>
[[Cilium|Cilia]] of eukaryotic cells can also produce chemotaxis; in this case, it is mainly a Ca<sup>2+</sup>-dependent induction of the [[microtubule|microtubular]] system of the [[basal body]] and the beat of the 9&nbsp;+&nbsp;2 microtubules within cilia. The orchestrated beating of hundreds of cilia is synchronized by a submembranous system built between basal bodies.
The details of the signaling pathways are still not totally clear.

====Chemotaxis-related migratory responses====
[[Image:Chtxphenomen1.png|right|400 px|<div style="text-align: center;border:none">Chemotaxis related migratory responses</div>]]
Chemotaxis refers to the directional migration of cells in response to chemical gradients; several variations of chemical-induced migration exist as listed below. 
* ''[[Chemokinesis]]'' refers to an increase in cellular motility in response to chemicals in the surrounding environment. Unlike chemotaxis, the migration stimulated by chemokinesis lacks directionality, and instead increases environmental scanning behaviors.<ref>{{cite journal | vauthors = Becker EL | title = Stimulated neutrophil locomotion: chemokinesis and chemotaxis | journal = Archives of Pathology & Laboratory Medicine | volume = 101 | issue = 10 | pages = 509–13 | date = October 1977 | pmid = 199132 }}</ref> 
* In ''[[haptotaxis]]'' the [[gradient]] of the chemoattractant is expressed or bound on a surface, in contrast to the classical model of chemotaxis, in which the gradient develops in a soluble fluid.<ref name="pmid6030602">{{cite journal | vauthors = Carter SB | s2cid = 4212997 | title = Haptotaxis and the mechanism of cell motility | journal = Nature | volume = 213 | issue = 5073 | pages = 256–60 | date = January 1967 | pmid = 6030602 | doi = 10.1038/213256a0 | bibcode = 1967Natur.213..256C }}</ref> The most common biologically active haptotactic surface is the [[extracellular matrix]] (ECM); the presence of bound [[ligands]] is responsible for induction of transendothelial migration and [[angiogenesis]].
* ''[[Necrotaxis]]'' embodies a special type of chemotaxis when the chemoattractant molecules are released from [[necrosis|necrotic]] or [[apoptosis|apoptotic]] cells. Depending on the chemical character of released substances, necrotaxis can accumulate or repel cells, which underlines the pathophysiological significance of this phenomenon.

===Receptors===
In general, eukaryotic cells sense the presence of chemotactic stimuli through the use of 7-transmembrane (or serpentine) heterotrimeric [[G protein|G-protein]]-coupled receptors, a class representing a significant portion of the [[genome]].<ref>{{cite journal | vauthors = Kim JY, Haastert PV, Devreotes PN | title = Social senses: G-protein-coupled receptor signaling pathways in Dictyostelium discoideum | journal = Chemistry & Biology | volume = 3 | issue = 4 | pages = 239–243 | date = April 1996 | pmid = 8807851 | doi = 10.1016/s1074-5521(96)90103-9 | doi-access = free }}</ref> Some members of this gene superfamily are used in eyesight ([[rhodopsins]]) as well as in [[olfaction]] (smelling).<ref>{{cite journal | vauthors = Montell C | title = Visual transduction in Drosophila | journal = Annual Review of Cell and Developmental Biology | volume = 15 | issue = 1 | pages = 231–268 | date = November 1999 | pmid = 10611962 | doi = 10.1146/annurev.cellbio.15.1.231 | s2cid = 14193715 }}</ref><ref>{{Cite book | vauthors = Antunes G, Simoes de Souza FM | title = G Protein-Coupled Receptors - Signaling, Trafficking and Regulation | chapter = Olfactory receptor signaling | series = Methods in Cell Biology | volume = 132 | pages = 127–45 | date = 2016 | pmid = 26928542 | doi = 10.1016/bs.mcb.2015.11.003  | isbn = 9780128035955 }}</ref> The main classes of chemotaxis receptors are triggered by:
* Formyl peptides - [[formyl peptide receptor]]s (FPR), 
* [[Chemokines]] - [[chemokine receptor]]s (CCR or CXCR), and 
* [[Leukotrienes]] - [[leukotriene receptor]]s (BLT).<ref>{{cite journal | vauthors = Thomas MA, Kleist AB, Volkman BF | title = Decoding the chemotactic signal | journal = Journal of Leukocyte Biology | volume = 104 | issue = 2 | pages = 359–374 | date = August 2018 | pmid = 29873835 | pmc = 6099250 | doi = 10.1002/JLB.1MR0218-044 }}</ref>
However, induction of a wide set of membrane receptors (e.g., [[cyclic nucleotide]]s, [[amino acids]], [[insulin]], vasoactive peptides) also elicit migration of the cell.<ref>{{cite journal | vauthors = van Haastert PJ, De Wit RJ, Konijn TM | title = Antagonists of chemoattractants reveal separate receptors for cAMP, folic acid and pterin in Dictyostelium | journal = Experimental Cell Research | volume = 140 | issue = 2 | pages = 453–6 | date = August 1982 | pmid = 7117406 | doi = 10.1016/0014-4827(82)90139-2 | s2cid = 27784085 | url = https://pure.rug.nl/ws/files/14539904/1982ExpCellResvHaastert.pdf }}</ref>

====Chemotactic selection====
[[Image:chtxsel.png|right|300 px|<div style="text-align: center;border:none">Chemotactic selection</div>]]
While some chemotaxis receptors are expressed in the surface membrane with long-term characteristics, as they are determined genetically, others have short-term dynamics, as they are assembled ''ad hoc'' in the presence of the ligand.<ref>{{cite book | vauthors = Witzany G, Nowacki M |title=Biocommunication of Ciliates |date=2016 |publisher=Springer |isbn=978-3-319-32211-7 }}{{page needed|date=July 2020}}</ref> The diverse features of the chemotaxis receptors and ligands allows for the possibility of selecting chemotactic responder cells with a simple chemotaxis assay By [[chemotactic selection]], we can determine whether a still-uncharacterized molecule acts via the long- or the short-term receptor pathway.<ref>{{cite book | vauthors = Köhidai L |chapter=Chemotaxis as an Expression of Communication of Tetrahymena |pages=65–82 |chapter-url=https://books.google.com/books?id=KnFBDAAAQBAJ&pg=PA65 |doi=10.1007/978-3-319-32211-7_5 | veditors = Witzany G, Nowacki M |title=Biocommunication of Ciliates |date=2016 |publisher=Springer |isbn=978-3-319-32211-7 }}</ref> The term ''chemotactic selection'' is also used to designate a technique that separates eukaryotic or prokaryotic cells according to their chemotactic responsiveness to selector ligands.<ref>{{cite journal | vauthors = Köhidai L, Csaba G | s2cid = 33755476 | title = Chemotaxis and chemotactic selection induced with cytokines (IL-8, RANTES and TNF-alpha) in the unicellular Tetrahymena pyriformis | journal = Cytokine | volume = 10 | issue = 7 | pages = 481–6 | date = July 1998 | pmid = 9702410 | doi = 10.1006/cyto.1997.0328 }}</ref>{{primary source inline|date=March 2017}}{{primary source inline|date=March 2017}}

===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>