lipoxin receptors

Summary

Summary: Cell surface proteins that bind LIPOXINS with high affinity and trigger intracellular changes influencing the behavior of cells.

Top Publications

  1. Alvarez V, Coto E, Setien F, Gonzalez Roces S, Lopez Larrea C. Molecular evolution of the N-formyl peptide and C5a receptors in non-human primates. Immunogenetics. 1996;44:446-52 pubmed
    ..In all species the four genes were physically linked and we defined the relative orientation of the four genes in primates: C5aR>FPR1>FPR2 (FPRL1)>FPRL2. ..
  2. Le Y, Wetzel M, Shen W, Gong W, Rogers T, Henderson E, et al. Desensitization of chemokine receptor CCR5 in dendritic cells at the early stage of differentiation by activation of formyl peptide receptors. Clin Immunol. 2001;99:365-72 pubmed
    ..Our results indicate that the expression and functions of CCR5 in iDC can be attenuated by W peptide, which activates formyl peptide receptors, and suggest an approach to the design of novel anti-HIV-1 agents. ..
  3. Perretti M, Chiang N, La M, Fierro I, Marullo S, Getting S, et al. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nat Med. 2002;8:1296-302 pubmed
  4. Sawmynaden P, Perretti M. Glucocorticoid upregulation of the annexin-A1 receptor in leukocytes. Biochem Biophys Res Commun. 2006;349:1351-5 pubmed
  5. Menezes de Lima O, Kassuya C, Nascimento A, Henriques M, Calixto J. Lipoxin A4 inhibits acute edema in mice: implications for the anti-edematogenic mechanism induced by aspirin. Prostaglandins Other Lipid Mediat. 2006;80:123-35 pubmed
    ..Finally, the present study demonstrates that ATLs exert a very important role in the acute anti-edematogenic action of ASA. ..
  6. Bae Y, Lee H, Jo E, Kim J, Kang H, Ye R, et al. Identification of peptides that antagonize formyl peptide receptor-like 1-mediated signaling. J Immunol. 2004;173:607-14 pubmed
    ..WRW(4) is the first specific FPRL1 antagonist and is expected to be useful in the study of FPRL1 signaling and in the development of drugs against FPRL1-related diseases. ..
  7. Christophe T, Karlsson A, Dugave C, Rabiet M, Boulay F, Dahlgren C. The synthetic peptide Trp-Lys-Tyr-Met-Val-Met-NH2 specifically activates neutrophils through FPRL1/lipoxin A4 receptors and is an agonist for the orphan monocyte-expressed chemoattractant receptor FPRL2. J Biol Chem. 2001;276:21585-93 pubmed
    ..Taken together, the results indicate that neutrophils are activated by WKYMVM through FPRL1 and that FPRL2 is a chemotactic receptor transducing signals in myeloid cells. ..
  8. Gao J, Chen H, Filie J, Kozak C, Murphy P. Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse. Genomics. 1998;51:270-6 pubmed
    ..These results suggest that the FPR gene cluster has undergone differential expansion in mammals with FPRL2, Fpr-rs2, Fpr-rs3, Fpr-rs4, and Fpr-rs5 arising after divergence of human and mouse. ..
  9. Ying G, Iribarren P, Zhou Y, Gong W, Zhang N, Yu Z, et al. Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. J Immunol. 2004;172:7078-85 pubmed
    ..We conclude that Humanin shares human FPRL1 and mouse FPR2 with Abeta(42) and suggest that Humanin may exert its neuroprotective effects by competitively inhibiting the access of FPRL1 to Abeta(42). ..

More Information

Publications62

  1. Elagoz A, Henderson D, Babu P, Salter S, Grahames C, Bowers L, et al. A truncated form of CKbeta8-1 is a potent agonist for human formyl peptide-receptor-like 1 receptor. Br J Pharmacol. 2004;141:37-46 pubmed
    ..These interactions were shown to be via FPRL-1 by specific blockade of PMNs activation in the presence of an FPRL-1 antibody. ..
  2. Dahlgren C, Christophe T, Boulay F, Madianos P, Rabiet M, Karlsson A. The synthetic chemoattractant Trp-Lys-Tyr-Met-Val-DMet activates neutrophils preferentially through the lipoxin A(4) receptor. Blood. 2000;95:1810-8 pubmed
    ..The observation that exudated cells are primed in their response to WKYMVm suggests that FPRL1/LXA(4)R like FPR is stored in mobilizable organelles. (Blood. 2000;95:1810-1818) ..
  3. Ernst S, Lange C, Wilbers A, Goebeler V, Gerke V, Rescher U. An annexin 1 N-terminal peptide activates leukocytes by triggering different members of the formyl peptide receptor family. J Immunol. 2004;172:7669-76 pubmed
  4. Sahagun Ruiz A, Colla J, Juhn J, Gao J, Murphy P, McDermott D. Contrasting evolution of the human leukocyte N-formylpeptide receptor subtypes FPR and FPRL1R. Genes Immun. 2001;2:335-42 pubmed
    ..Thus FPR1 and FPRL1, though they originated from a common gene, appear to have undergone markedly different evolutionary events. ..
  5. Su S, Gong W, Gao J, Shen W, Murphy P, Oppenheim J, et al. A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells. J Exp Med. 1999;189:395-402 pubmed
    ..In contrast, SAA was not a ligand or agonist for FPR, the high affinity fMLP receptor. Thus, SAA is the first chemotactic ligand identified for FPRL1. Our results suggest that FPRL1 mediates phagocyte migration in response to SAA. ..
  6. Christophe T, Karlsson A, Rabiet M, Boulay F, Dahlgren C. Phagocyte activation by Trp-Lys-Tyr-Met-Val-Met, acting through FPRL1/LXA4R, is not affected by lipoxin A4. Scand J Immunol. 2002;56:470-6 pubmed
    ..We conclude that LXA4 is unable to affect the WKYMVM-induced signalling through FPRL1 and suggest that it acts through a receptor different from FPRL1. ..
  7. Le Y, Murphy P, Wang J. Formyl-peptide receptors revisited. Trends Immunol. 2002;23:541-8 pubmed
  8. Betten A, Dahlgren C, Hermodsson S, Hellstrand K. Histamine inhibits neutrophil NADPH oxidase activity triggered by the lipoxin A4 receptor-specific peptide agonist Trp-Lys-Tyr-Met-Val-Met. Scand J Immunol. 2003;58:321-6 pubmed
    ..Our data suggest that histamine downregulates FPRL1- and FPR-induced NADPH oxidase activity upstream of protein kinase C (PKC) and downstream of the separation of the peptide-induced signal into granule secretion and oxidase activation. ..
  9. Bylund J, Karlsson A, Boulay F, Dahlgren C. Lipopolysaccharide-induced granule mobilization and priming of the neutrophil response to Helicobacter pylori peptide Hp(2-20), which activates formyl peptide receptor-like 1. Infect Immun. 2002;70:2908-14 pubmed
    ..These results suggest that the mechanism behind the LPS-induced priming of FPRL1-mediated responses lies at the level of granule (receptor) mobilization. ..
  10. Durstin M, Gao J, Tiffany H, McDermott D, Murphy P. Differential expression of members of the N-formylpeptide receptor gene cluster in human phagocytes. Biochem Biophys Res Commun. 1994;201:174-9 pubmed
    ..In contrast, FPRL2 RNA is detectable in monocytes but not in neutrophils, and its product could not be activated by N-formylpeptides. Thus, the regulation of FPRL2 gene expression in vivo differs from FPR1 and FPRL1. ..
  11. Takano T, Fiore S, Maddox J, Brady H, Petasis N, Serhan C. Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Exp Med. 1997;185:1693-704 pubmed
    ..These findings provide direct in vivo evidence for an anti-inflammatory action for both aspirin-triggered LXA4 and LXA4 stable analogues and their site of action in vivo. ..
  12. Maddox J, Hachicha M, Takano T, Petasis N, Fokin V, Serhan C. Lipoxin A4 stable analogs are potent mimetics that stimulate human monocytes and THP-1 cells via a G-protein-linked lipoxin A4 receptor. J Biol Chem. 1997;272:6972-8 pubmed
    ..Moreover, they provide additional evidence that the LXA4 stable analogs retain selective bioactivity in monocytes and are valuable instruments for examining the functions and modes of action of LXA4. ..
  13. Chiang N, Gronert K, Clish C, O Brien J, Freeman M, Serhan C. Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusion. J Clin Invest. 1999;104:309-16 pubmed
    ..Moreover, LXA4 and ATL counter BLTR-amplified networks, revealing a novel protective role for LX and ATL in stress responses that has applications in perioperative medicine. ..
  14. Deng X, Ueda H, Su S, Gong W, Dunlop N, Gao J, et al. A synthetic peptide derived from human immunodeficiency virus type 1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R. Blood. 1999;94:1165-73 pubmed
    ..This may explain, at least in part, the initial activation of innate immune responses in HIV-1-infected patients followed by immune suppression. ..
  15. Le Y, Yang Y, Cui Y, Yazawa H, Gong W, Qiu C, et al. Receptors for chemotactic formyl peptides as pharmacological targets. Int Immunopharmacol. 2002;2:1-13 pubmed
    ..Thus, by interacting with a variety of exogenous and host-derived agonists, formyl peptide receptors may play important roles in proinflammatory and immunological diseases and constitute a novel group of pharmacological targets. ..
  16. Murphy P, Ozcelik T, Kenney R, Tiffany H, McDermott D, Francke U. A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family. J Biol Chem. 1992;267:7637-43 pubmed
    ..Moreover, discovery of the FPRL1 receptor indicates the existence of another as yet unidentified peptide that may recruit neutrophils to sites of inflammation. ..
  17. Gronert K, Gewirtz A, Madara J, Serhan C. Identification of a human enterocyte lipoxin A4 receptor that is regulated by interleukin (IL)-13 and interferon gamma and inhibits tumor necrosis factor alpha-induced IL-8 release. J Exp Med. 1998;187:1285-94 pubmed
    ..Taken together, these results identify an endogenous pathway for downregulating mucosal inflammatory events and suggest a potential therapeutic benefit for LXA4 stable analogs. ..
  18. Yang D, Chen Q, Le Y, Wang J, Oppenheim J. Differential regulation of formyl peptide receptor-like 1 expression during the differentiation of monocytes to dendritic cells and macrophages. J Immunol. 2001;166:4092-8 pubmed
    ..The fact that macrophages rather than myeloid DC express functional FPRL1 suggests that this chemotactic receptor may be more involved in inflammatory reactions and innate host defense than in adaptive immune responses. ..
  19. Le Y, Oppenheim J, Wang J. Pleiotropic roles of formyl peptide receptors. Cytokine Growth Factor Rev. 2001;12:91-105 pubmed
    ..These new findings have greatly expanded the functional scope of the formyl peptide receptors and call for more in-depth investigation of the role of these receptors in pathophysiological conditions. ..
  20. Li B, Wetzel M, Mikovits J, Henderson E, Rogers T, Gong W, et al. The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1. Blood. 2001;97:2941-7 pubmed
    ..Blood. 2001;97:2941-2947) ..
  21. Betten A -, Bylund J, Christophe T, Cristophe T, Boulay F, Romero A, et al. A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis. J Clin Invest. 2001;108:1221-8 pubmed
    ..These novel mechanisms may be subject to local, histaminergic regulation in the gastric mucosa. ..
  22. Chiang N, Fierro I, Gronert K, Serhan C. Activation of lipoxin A(4) receptors by aspirin-triggered lipoxins and select peptides evokes ligand-specific responses in inflammation. J Exp Med. 2000;191:1197-208 pubmed
  23. Gavins F, Yona S, Kamal A, Flower R, Perretti M. Leukocyte antiadhesive actions of annexin 1: ALXR- and FPR-related anti-inflammatory mechanisms. Blood. 2003;101:4140-7 pubmed
    ..The present findings demonstrate that endogenous regulatory autocoids such as lipoxin A(4) and annexin 1-derived peptides function to disengage adherent cells during cell-cell interactions. ..
  24. Ernst S, Zobiack N, Boecker K, Gerke V, Rescher U. Agonist-induced trafficking of the low-affinity formyl peptide receptor FPRL1. Cell Mol Life Sci. 2004;61:1684-92 pubmed
    ..Thus, ligand-bound FPRL1 undergoes primarily clathrin-mediated and dynamin-dependent endocytosis and the receptor recycles via a rapid PI3-kinase-sensitive route as well as pathways involving perinuclear recycling endosomes. ..
  25. Koga T, Torigoshi T, Motokawa S, Miyashita T, Maeda Y, Nakamura M, et al. Serum amyloid A-induced IL-6 production by rheumatoid synoviocytes. FEBS Lett. 2008;582:579-85 pubmed publisher
    ..Our findings demonstrate that SAA is a significant inducer of IL-6, which is critically involved in RA pathogenesis. ..
  26. Maderna P, Godson C. Taking insult from injury: lipoxins and lipoxin receptor agonists and phagocytosis of apoptotic cells. Prostaglandins Leukot Essent Fatty Acids. 2005;73:179-87 pubmed
    ..Here we review the mechanisms underlying recognition and engulfment of apoptotic cells and regulation of these processes by lipoxins and lipoxin receptor agonists. ..
  27. Nedellec R, Coetzer M, Shimizu N, Hoshino H, Polonis V, Morris L, et al. Virus entry via the alternative coreceptors CCR3 and FPRL1 differs by human immunodeficiency virus type 1 subtype. J Virol. 2009;83:8353-63 pubmed publisher
    ..These data may provide insight into development of resistance to CCR5-targeted entry inhibitors and alternative entry pathways for each HIV-1 subtype. ..
  28. Hayhoe R, Kamal A, Solito E, Flower R, Cooper D, Perretti M. Annexin 1 and its bioactive peptide inhibit neutrophil-endothelium interactions under flow: indication of distinct receptor involvement. Blood. 2006;107:2123-30 pubmed
    ..These findings demonstrate for the first time distinct mechanisms of action for ANXA1 and its N-terminal peptide Ac2-26. ..
  29. Tsuruki T, Yoshikawa M. Orally administered FPRL1 receptor agonist peptide MMK-1 inhibits etoposide-induced alopecia by a mechanism different from intraperitoneally administered MMK-1. Peptides. 2006;27:820-5 pubmed
    ..These results suggest that MMK-1 bound to FPRL1 receptor might suppress etoposide-induced apoptosis of hair follicle cells and alopecia by way of PGE2 release and NF-kappaB activation. ..
  30. Grond Ginsbach C, Hummel M, Wiest T, Horstmann S, Pfleger K, Hergenhahn M, et al. Gene expression in human peripheral blood mononuclear cells upon acute ischemic stroke. J Neurol. 2008;255:723-31 pubmed publisher
    ..However, comparing AIS patients with healthy control subjects revealed measurable differences in PDE4D and in inflammatory response genes when considered as a set. ..
  31. Pivot Pajot C, Chouinard F, El Azreq M, Harbour D, Bourgoin S. Characterisation of degranulation and phagocytic capacity of a human neutrophilic cellular model, PLB-985 cells. Immunobiology. 2010;215:38-52 pubmed publisher
    ..Altogether our results reinforce the fact that depending on the differentiating agent used, PLB-985 cells represent a useful model to study neutrophil functions and to bypass difficulties inherent to these primary cells. ..
  32. Peskar B, Ehrlich K, Schuligoi R, Peskar B. Role of lipoxygenases and the lipoxin A(4)/annexin 1 receptor in ischemia-reperfusion-induced gastric mucosal damage in rats. Pharmacology. 2009;84:294-9 pubmed publisher
    ..The results suggest that not only cyclooxygenases, but also lipoxygenases have a role in limiting gastric mucosal damage during ischemia-reperfusion. ..
  33. Kam A, Liu A, Wong Y. Formyl peptide-receptor like-1 requires lipid raft and extracellular signal-regulated protein kinase to activate inhibitor-kappa B kinase in human U87 astrocytoma cells. J Neurochem. 2007;103:1553-66 pubmed
    ..Taken together, these results demonstrate that FPRL-1 is capable of activating NFkappaB signaling through IKK phosphorylation and this may serve as a useful therapeutical target for FPRL-1-related diseases. ..
  34. Bae Y, Song J, Kim Y, He R, Ye R, Kwak J, et al. Differential activation of formyl peptide receptor signaling by peptide ligands. Mol Pharmacol. 2003;64:841-7 pubmed
    ..Our results suggest that WKGMVm and WKRMVm may be useful model for further development of pharmacological agents that selectively activate FPR-mediated functions. ..
  35. Brink C, Dahlen S, Drazen J, Evans J, Hay D, Nicosia S, et al. International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors. Pharmacol Rev. 2003;55:195-227 pubmed
    ..The aim of this review is to provide the molecular evidence as well as the properties and significance of the leukotriene and lipoxin receptors, which has lead to the present nomenclature.
  36. Kim Y, Lee B, Kim O, Bae Y, Lee T, Suh P, et al. Pituitary adenylate cyclase-activating polypeptide 27 is a functional ligand for formyl peptide receptor-like 1. J Immunol. 2006;176:2969-75 pubmed
    ..Taken together, our study suggests that PACAP27 activates phagocytes via FPRL1 activation, and that this results in proinflammatory behavior, involving chemotaxis and the up-regulation of CD11b. ..
  37. de Paulis A, Montuori N, Prevete N, Fiorentino I, Rossi F, Visconte V, et al. Urokinase induces basophil chemotaxis through a urokinase receptor epitope that is an endogenous ligand for formyl peptide receptor-like 1 and -like 2. J Immunol. 2004;173:5739-48 pubmed
    ..Thus, uPA is a potent chemoattractant for basophils that seems to act through exposure of the chemotactic uPAR epitope uPAR84-95, which is an endogenous ligand for FPRL2 and FPRL1. ..
  38. Peters Golden M. 'Good' lipids for asthma. Nat Med. 2002;8:931-2 pubmed
  39. Ariel A, Chiang N, Arita M, Petasis N, Serhan C. Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated kinase-dependent TNF-alpha secretion from human T cells. J Immunol. 2003;170:6266-72 pubmed
    ..Moreover, they provide potential counterregulatory signals in communication(s) between the innate and acquired immune systems. ..
  40. Gavins F, Sawmynaden P, Chatterjee B, Perretti M. A twist in anti-inflammation: annexin 1 acts via the lipoxin A4 receptor. Prostaglandins Leukot Essent Fatty Acids. 2005;73:211-9 pubmed
  41. Pliyev B, Menshikov M. Release of the soluble urokinase-type plasminogen activator receptor (suPAR) by activated neutrophils in rheumatoid arthritis. Inflammation. 2010;33:1-9 pubmed publisher
  42. Kam A, Tse T, Kwan D, Wong Y. Formyl peptide receptor like 1 differentially requires mitogen-activated protein kinases for the induction of glial fibrillary acidic protein and interleukin-1alpha in human U87 astrocytoma cells. Cell Signal. 2007;19:2106-17 pubmed
    ..We have thus identified a possible linkage among FPRL1, MAPKs, astrocytic activation and the inflammatory response. ..
  43. Afkhami Goli A, Noorbakhsh F, Keller A, Vergnolle N, Westaway D, Jhamandas J, et al. Proteinase-activated receptor-2 exerts protective and pathogenic cell type-specific effects in Alzheimer's disease. J Immunol. 2007;179:5493-503 pubmed
  44. Cheng X, Lu S, Cui Y. ECRG2 regulates ECM degradation and uPAR/FPRL1 pathway contributing cell invasion/migration. Cancer Lett. 2010;290:87-95 pubmed publisher
    ..Together, our results provide evidence that ECRG2 regulates invasion/migration partly through ECM degradation and uPA/uPAR/FPRL1 pathway, and may represent a novel therapeutic target for cancer. ..
  45. Levy B, De Sanctis G, Devchand P, Kim E, Ackerman K, Schmidt B, et al. Lipoxins and aspirin-triggered lipoxins in airway responses. Adv Exp Med Biol. 2003;525:19-23 pubmed
    ..Moreover, these results indicate that LX's play pivotal and previously unappreciated roles in regulating allergy and pulmonary inflammation. ..
  46. Lee H, Kim S, Shim J, Lee S, Lee H, Cho K, et al. Serum amyloid A induces CCL2 production via formyl peptide receptor-like 1-mediated signaling in human monocytes. J Immunol. 2008;181:4332-9 pubmed
    ..These results suggest that SAA and FPRL1 offer a developmental starting point for the treatment of atherosclerosis. ..
  47. Rabiet M, Huet E, Boulay F. Human mitochondria-derived N-formylated peptides are novel agonists equally active on FPR and FPRL1, while Listeria monocytogenes-derived peptides preferentially activate FPR. Eur J Immunol. 2005;35:2486-95 pubmed
    ..We identified novel mitochondrial host-derived agonists for human N-formyl-peptide receptors that might play a role in inflammatory or degenerative processes linked to their stimulation. ..
  48. Perretti M, D Acquisto F. Novel aspects of annexin 1 and glucocorticoid biology: intersection with nitric oxide and the lipoxin receptor. Inflamm Allergy Drug Targets. 2006;5:107-14 pubmed
    ..The two mediators/targets here illustrated are to be taken as examples of the clues that the study of anti-inflammation might give to the pharmaceutical industry for innovative drug discovery. ..
  49. Cui Y, Le Y, Zhang X, Gong W, Abe K, Sun R, et al. Up-regulation of FPR2, a chemotactic receptor for amyloid beta 1-42 (A beta 42), in murine microglial cells by TNF alpha. Neurobiol Dis. 2002;10:366-77 pubmed
    ..TNF alpha concomitantly down-regulated microglial response to the chemokine SDF-1 alpha. Thus, by selectively up-regulating FPR2 in microglia, TNF alpha has the capacity to amplify host response in inflammatory diseases in the CNS. ..
  50. Fujita T, Zawawi K, Kurihara H, Van Dyke T. CD38 cleavage in fMLP- and IL-8-induced chemotaxis is dependent on p38 MAP kinase but independent of p44/42 MAP kinase. Cell Signal. 2005;17:167-75 pubmed
    ..Activation of the protease for cleavage appears to be a postreceptor event that is dependent on p38 MAP kinase signaling. ..
  51. Jo S, Yun J, Kim J, Lee C, Baek S, Bae Y. Serum amyloid A induces WISH cell apoptosis. Acta Pharmacol Sin. 2007;28:73-80 pubmed
    ..SAA is a novel inducer for WISH cell apoptosis, and the PTX-insensitive pathway is involved in the process. ..
  52. O Hara R, Murphy E, Whitehead A, Fitzgerald O, Bresnihan B. Local expression of the serum amyloid A and formyl peptide receptor-like 1 genes in synovial tissue is associated with matrix metalloproteinase production in patients with inflammatory arthritis. Arthritis Rheum. 2004;50:1788-99 pubmed
    ..Therapeutic targeting of A-SAA, or FPRL1, may modulate pathophysiologic pathways that are associated with matrix degradation in patients with RA and other forms of progressive inflammatory arthritis. ..
  53. Filep J, El Kebir D. Neutrophil apoptosis: a target for enhancing the resolution of inflammation. J Cell Biochem. 2009;108:1039-46 pubmed publisher