Chemokiny w patogenezie udaru niedokrwiennego mózgu

• Authors: Anna Cisowska-Maciejewska , Maria Konarska , Andrzej Głąbiński

Title variants

EN

Chemokines in pathogenesis of ischaemic stroke

• Languages of publication: EN PL

Abstracts

EN

Chemokines are cytokines which attract certain supopulations of leukocytes. They constitute the family of 50 proteins of low molecular weight (8-12 kDa). They are divided into four groups: CXC, CC, CX3C, C. Chemokines acts via receptors C-R, CC-R, CXC-R, CX3C-R. About 20 receptors for chemokines are described so far. Many chemokines may bind to one receptor and one chemokine may target more than one receptor. Chemokines exert many physiological activities as well as can be involved in pathogenesis of ischaemic stroke. The main role of chemokines is engagement into development of inflammatory reaction. Chemokines are engaged also in maturation and function of immunological system as well. Further they are engaged into pathogenesis of many other pathologies like myocardial infarction, ischaemic stroke, multiple sclerosis, Alzheimer’s disease, brain tumours. The increased expression of chemokines in the brain is induced by different stimulus as ischaemia, axonal damage, or presence of neurotoxic substances. Till now, many chemokines were investigated because of their participation in development of atheromatous plaque in carotid arteries of animal models and humans is increased as well. Expression of selected chemokines on atheromatous plaques from patients operated because of critical stenosis of internal carotid artery was described. Chemokines belonging to different classes (CCL2, CXCL1, CX3CL1, CCL5, CXCL1) with proven but not finally investigated participation in atherogenesis and its complications were analysed. Furthermore concentration of selected chemokines in peripheral blood and expression of some chemokines on peripheral blood mononuclear cells from patients with and without restenosis was also published. Chemokines are engaged also in complications of atherosclerosis such as ischaemic stroke or myocardial infarction. The goal of this review was to highlight the role of various chemokines and their receptors in such conditions. Experimental data with knock-out genes or agonists of chemokine receptors give the hope to development of new therapies for brain ischaemia.

PL

Chemokiny są cytokinami działającymi na określone subpopulacje leukocytów. Stanowią rodzinę ponad 50 białek o stosunkowo małej masie cząsteczkowej (8-12 kDa). Wyróżniamy kilka grup chemokin: CXC, CC, CX3C, C. Działają one na komórki docelowe za pośrednictwem odpowiednich receptorów C-R, CC-R, CXC-R, CX3C-R. Zidentyfikowano dotąd około 20 receptorów dla chemokin. Wykazano, że z danym receptorem mogą się zwykle wiązać różne chemokiny, a dana chemokina może wykazywać powinowactwo do więcej niż jednego receptora. Chemokiny są zaangażowane w szereg procesów fizjologicznych, m.in. w patogenezę udaru niedokrwiennego mózgu. Zasadnicza rola chemokin polega na ich udziale w rozwoju reakcji zapalnej. Chemokiny odgrywają również kluczową rolę w dojrzewaniu i funkcjonowaniu układu immunologicznego. Ponadto są zaangażowane w patogenezę wielu różnorodnych schorzeń, takich jak zawał mięśnia sercowego, udar mózgu, stwardnienie rozsiane, choroba Alzheimera, nowotwory mózgu. Zwiększona ekspresja chemokin w mózgu jest następstwem działania różnorodnych bodźców, takich jak niedokrwienie, uszkodzenie aksonalne czy obecność substancji o działaniu neurotoksycznym. Dotychczas przebadano wiele chemokin pod kątem ich udziału w rozwoju blaszki miażdżycowej w tętnicach szyjnych, zarówno na materiale zwierzęcym, jak i na materiale ludzkim. Oceniano między innymi ekspresję wybranych chemokin w blaszkach miażdżycowych pobranych od pacjentów z krytycznym zwężeniem tętnicy szyjnej wewnętrznej poddanych zabiegowi endarterektomii. Analizowano chemokiny należące do różnych klas o udowodnionym, ale nie do końca zbadanym udziale w patogenezie miażdżycy i jej powikłań (tj. CCL2, CXCL1, CX3CL1, CCL5, CXCL1). Ponadto oceniano stężenie wybranych chemokin we krwi obwodowej oraz ekspresję wybranych chemokin na komórkach jednojądrzastych krwi obwodowej u pacjentów z restenozą i bez niej. Są one także zaangażowane w patogenezę rozwoju powikłań blaszki miażdżycowej, tj. udaru niedokrwiennego mózgu czy zawału mięśnia sercowego. W niniejszej pracy przedstawiono dane dotyczące udziału różnych chemokin i ich receptorów. Wyniki badań eksperymentalnych z wyciszaniem genów czy zastosowaniem agonistów receptorów chemokinowych pozwalają mieć nadzieję na rozwój nowych terapii chorób naczyniowych.

Keywords

EN

atherosclerosis; cervical artery; chemokine receptors; chemokines; chemokiny; ischaemic stroke; miażdżyca; receptory chemokinowe; tętnica szyjna; udar niedokrwienny

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Aktualności Neurologiczne
• Year: 2010
• Volume: 10
• Issue: 2
• Pages: 79 - 84

Contributors

author

Anna Cisowska-Maciejewska

• Oddział Kliniczny Propedeutyki Neurologicznej, Uniwersytet Medyczny, ul. Pabianicka 62, 93-513 Łódź

author

Maria Konarska

• Oddział Kliniczny Propedeutyki Neurologicznej, Uniwersytet Medyczny, ul. Pabianicka 62, 93-513 Łódź

author

Andrzej Głąbiński

• Oddział Kliniczny Propedeutyki Neurologicznej, Uniwersytet Medyczny, ul. Pabianicka 62, 93-513 Łódź

References

• 1. Rollins B.J.: Chemokines. Blood 1997; 90: 909-928.
• 2. Clark-Lewis I., Kim K.S., Rajarathnam K. i wsp.: Structure-activity relationships of chemokines. J. Leukoc. Biol. 1995; 57: 703-711.
• 3. Clore G.M., Gronenborn AM.: Three-dimensional structures of alpha and beta chemokines. FASEB J. 1995; 9: 57-62.
• 4. Vandercappellen J., Van Damme J., Struyf S.: The role of CXC chemokines and their receptors in cancer. Cancer Lett. 2008; 267: 226-244.
• 5. Cochran B.H., Reffel A.C., Stiles C.D.: Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell 1983; 933: 939.
• 6. Richmond A., Belentien E., Thomas H.G. i wsp.: Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin. EMBO J. 1988; 7: 2025-2033.
• 7. Zaremba J., Ilkowski J., Losy J.: Serial measurements of levels of the chemokines CCL2, CCL3 and CCL5 in serum of patients with acute ischaemic stroke. Folia Neuropathol. 2006: 44: 282-289.
• 8. Jiang Y., Beller D.I., Frendl G., Graves D.T: Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes. J. Immunol. 1992; 148: 2423-2428.
• 9. Vaddi K., Newton R.C.: Regulation of monocyte integrin expression by β-family chemokines. J. Immunol. 1994; 153: 4721.
• 10. Carr M.W, Roth S.J., Luther E. i wsp.: Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant Proc. Natl Acad. Sci. USA 1994; 91: 3652-3656.
• 11. Loetscher P, Seitz M., Clark-Lewis I. i wsp.: Activation of NK cells by CC chemokines. Chemotaxis, Ca2+ mobilization, and enzyme release. J. Immunol. 1996; 156: 322-327.
• 12. Allavena P, Bianchi G., Zhou D. i wsp.: Induction of natural killer cell migration by monocyte chemotactic protein-1, -2 and -3. Eur. J. Immunol. 1994; 24: 3233-3236.
• 13. Bischoff S.C., Krieger M., Brunner T, Dahinden C.A.: Monocyte chemotactic protein 1 is a potent activator of human basophils. J. Exp. Med. 1992; 175: 1271-1275.
• 14. Kuna P, Reddigari S.R., Rucinski D. i wsp.: Monocyte chemotactic and activating factor is a potent histamine-releasing factor for human basophils. J. Exp. Med. 1992; 175: 489-493.
• 15. Alam R., Lett-Brown M.A., Forsythe PA. i wsp.: Monocyte chemotactic and activating factor is a potent histamine-releasing factor for basophils. J. Clin. Invest. 1992; 89: 723-728.
• 16. Uguccioni M., D’Apuzzo M., Loetscher M. i wsp.: Actions of the chemotactic cytokines MCP-1, MCP-2, MCP-3, RANTES, MIP-1α and MIP-1β on human monocytes. Eur. J. Immunol. 1995; 25: 64-68.
• 17. Van Damme J., Proost P, Lenaerts J.P, Opdenakker G.: Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. J. Exp. Med. 1992; 176: 59-65.
• 18. Sozzani S., Locati M., Zhou D. i wsp.: Receptors, signal transduction, and spectrum of action of monocyte chemotactic protein-1 and related chemokines. J. Leukoc. Biol. 1995; 57: 788-794.
• 19. Proost P, Wuyts A., Van Damme J.: Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1. J. Leukoc. Biol. 1996; 59: 67-74.
• 20. Dahinden C.A., Geiser T, Brunner T i wsp.: Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil-activating chemokine. J. Exp. Med. 1994; 179: 751-756.
• 21. Weber M., Uguccioni M., Ochensberger B. i wsp.: Monocyte chemotactic protein MCP-2 activates human basophil and eosinophil leukocytes similar to MCP-3. J. Immunol. 1995; 154: 4166-4172.
• 22. Noso N., Proost P, Van Damme J., Schroder J.M.: Human monocyte chemotactic proteins-2 and 3 (MCP-2 and MCP-3) attract human eosinophils and desensitize the chemotactic responses towards RANTES. Biochem. Biophys. Res. Commun. 1994; 200: 1470-1476.
• 23. Sozzani S., Sallusto F, Luini W i wsp.: Migration of dendritic cells in reponse to formyl peptides, C5a, and a distinct set of chemokines. J. Immunol. 1995; 155: 3292-3295.
• 24. Uguccioni M., Loetscher P, Forssmann U. i wsp.: Monocyte chemotactic protein 4 (MCP-4), a novel structural and functional analogue of MCP-3 and eotaxin. J. Exp. Med. 1996; 183: 2379-2384.
• 25. Sarafi M.N., Garcia-Zepeda E.A., MacLean J.A. i wsp.: Murine monocyte chemoattractant protein (MCP)-5: a novel CC chemokine that is a structural and functional homologue of human MCP-1. J. Exp. Med. 1997; 185: 99-109.
• 26. Jia G.Q., Gonzalo J.A., Lloyd C. i wsp.: Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation. J. Exp. Med. 1996; 184: 1939-1951.
• 27. Banisadr G., Rostène W, Kitabgi P, Parsadaniantz SM.: Chemokines and brain functions. Curr. Drug Targets Inflamm. Allergy 2005; 4: 387-399.
• 28. Murphy PM.: International Union of Pharmacology. XXX. Update on chemokine receptor nomenclature. Pharmacol. Rev. 2002; 54: 227-229.
• 29. Clark-Lewis I., Schumacher C., Baggiolini M., Moser B.: Structure-activity relationships of interleukin-8 determined using chemically synthesized analogs. Critical role of NH2-terminal residues and evidence for uncoupling of neutrophil chemotaxis, exocytosis, and receptor binding activities. J. Biol. Chem. 1991; 266: 23128-23134.
• 30. Proudfoot A.E., Power C.A., Hoogewerf A.J. i wsp.: Extension of recombinant human RANTES by the retention of the initiating methionine produces a potent antagonist. J. Biol. Chem. 1996; 271: 2599-2603.
• 31. Jones SA, Moser B., Thelen M.: A comparison of post-receptor signal transduction events in Jurkat cells transfected with either IL-8R1 or IL-8R2. Chemokine mediated activation of p42/p44 MAP-kinase (ERK-2). FEBS Lett. 1995; 364: 211-214.
• 32. Knall C., Young S., Nick JA i wsp.: Interleukin-8 regulation of the Ras/Raf/mitogen-activated protein kinase pathway in human neutrophils. J. Biol. Chem. 1996; 271: 2832-2838.
• 33. Bajetto A., Barbero S., Bonavia R. i wsp.: Stromal cell-derived factor-1α induces astrocyte proliferation through the activation of extracellular signal-regulated kinases 1/2 pathway. J. Neurochem. 2001; 77: 1226-1236.
• 34. Minami M., Satoh M.: Role of chemokines in ischemic neuronal stress. Neuromolecular Med. 2005; 7: 149-155.
• 35. Kim J.S., Gautam S.C., Chopp M. i wsp.: Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 after focal cerebral ischemia in the rat. J. Neuroimmu-nol. 1995; 56: 127-134.
• 36. Jiang L., Newman M., Saporta S. i wsp.: MIP-1α and MCP-1 induce migration of human umbilical cord blood cells in models of stroke. Curr. Neurovasc. Res. 2008; 5: 118-124.
• 37. Takami S., Minami M., Nagata I. i wsp.: Chemokine receptor antagonist peptide, viral MIP-II, protects the brain against focal cerebral ischemia in mice. J. Cereb. Blood Flow Metab. 2001; 21: 1430-1435.
• 38. Stamatovic S.M., Shakui P, Keep R.F. i wsp.: Monocyte chemoattractant protein-1 regulation of blood-brain barrier permeability. J. Cereb. Blood Flow Metab. 2005; 25: 593-606.
• 39. Dimitrijevic O.B., Stamatovic S.M., Keep R.F., Andjelkovic A.V: Effects of the chemokine CCL2 on blood-brain barrier permeability during ischemia-reperfusion injury. J. Cereb. Blood Flow Metab. 2006; 26: 797-810.
• 40. Hughes PM., Allegrini PR., Rudin M. i wsp.: Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model. J. Cereb. Blood Flow Metab. 2002; 22: 308-317.
• 41. Kumai Y., Ooboshi H., Takada J. i wsp.: Anti-monocyte chemoattractant protein-1 gene therapy protects against focal brain ischemia in hypertensive rats. J. Cereb. Blood Flow Metab. 2004: 24: 1359-1368.
• 42. Terao S., Yilmaz G., Stokes K.Y. i wsp.: Blood cell-derived RAN-TES mediates cerebral microvascular dysfunction, inflammation, and tissue injury after focal ischemia-reperfusion. Stroke 2008; 39: 2560-2570.
• 43. Losy J., Zaremba J., Skrobański P: CXCL1 (GRO-alpha) chemokine in acute ischaemic stroke patients. Folia Morphol. 2006; 65: 1-5.
• 44. Veillard N.R., Steffens S., Burger F. i wsp.: Differential expression patterns of proinflammatory and antiinflammatory mediators during atherogenesis in mice. Arterioscler. Thromb. Vasc. Biol. 2004; 24: 2339-2344.
• 45. Tarozzo G., Campanella M., Ghiani M. i wsp.: Expression of fractalkine and its receptor, CX3CR1, in response to ischaemia-reperfusion brain injury in the rat. Eur. J. Neurosci. 2002; 15: 1663-1668.
• 46. Arekelian A.A., Boiadzhian A.S., Petrek M. i wsp.: The role of cytokines in ischemic stroke. Klin. Med. (Mosk.) 2005; 83: 22-24.
• 47. Losy J., Zaremba J.: Monocyte chemoattractant protein-1 is increased in the cerebro-spinal fluid of patients with ischemic stroke. Stroke 2001; 32: 2695-2696.
• 48. Losy J., Zaremba J., Skrobański P: CXCL1 (GRO-alpha) che-mokine in acute ischaemic stroke patients. Folia Neuropathol. 2005; 43: 97-102.
• 49. Zaremba J., Skrobański P, Losy J.: The level of chemokine CXCL5 in the cerebrospinal fluid is increased during the first 24 hours of ischemic stroke and correlates with the size of early brain damage. Folia Morphol. 2006; 65: 1-5.
• 50. Grau A.J., Reis A., Buggle F. i wsp.: Monocyte function and plasma levels of interleukin-8 in acute ischemic stroke. J. Neurol. Sci. 2001; 192: 41-47.
• 51. Nelken NA, Coughlin S.R., Gordon D., Wilcox J.N.: Monocyte chemoattractant protein-1 in human atheromatous plaques. J. Clin. Invest. 1991; 88: 1121-1127.
• 52. Gerszten R.E., Garcia-Zepeda EA, Lim Y.C. i wsp.: MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 1999; 398: 718-723.
• 53. Störk S., Baumann K., von Schacky C., Angerer P.: The effects of 17β-estradiol on MCP1 serum levels in postmenopausal women. Cardiovasc. Res. 2002; 53: 642-649.
• 54. Cushing S.D., Berliner JA, Valente A.J. i wsp.: Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc. Natl. Acad. Sci. USA 1990; 87: 5134-5138.
• 55. Boring L., Gosling J., Cleary M., Charo I.F.: Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 1998; 394: 894-897.
• 56. Mosedale D.E., Smith D.J., Aitken S. i wsp.: Circulating levels of MCP-1 and eotaxin are not associated with presence of atherosclerosis or previous myocardial infarction. Atherosclerosis 2005; 183: 268-274.
• 57. Reynolds M.A., Kirchick H.J., Dahlen J.R i wsp.: Early biomarkers of stroke. Clin. Chem. 2003; 49: 1733-1739.
• 58. Pervin S., Singh R., Rosenfeld M.E. i wsp.: Estradiol suppresses MCP-1 expression In vivo: implications for atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 1998; 18: 1575-1582.
• 59. Seli E., Selam B., Mor G. i wsp.: Estradiol regulates monocyte chemotactic protein-1 in human coronary artery smooth muscle cells: a mechanism for its antiatherogenic effect. Menopause 2001; 8: 296-301.
• 60. Tedeschi-Reiner E., Reiner Z.: Estrogens and risk for onset of atherosclerosis. Lijec. Vjesn. 2001; 123: 135-141.
• 61. Bazan J.F, Bacon K.B., Hardiman G. i wsp.: A new class of membrane-bound chemokine with a CX3C motif. Nature 1997; 385: 640-644.
• 62. Imai T, Hieshima K., Haskell C. i wsp.: Identification and molecular characterization of fractalkine receptor CX3CR1 which mediates both leukocyte migration and adhesion. Cell 1997; 91: 521-530.
• 63. Ludwig A., Berkhout T, Moores K. i wsp.: Fractalkine is expressed by smooth muscle cells in response to INF-gamma and TNF-alpha and is modulated by metalloproteinase activity. J. Immunol. 2002; 168: 604-612.
• 64. Lavergne E., Labreuche J., Daoudi M. i wsp.: Adverse associations between CX3CR1 polymorphisms and risk of cardiovascular disease. Arterioscler. Thromb. Vasc. Biol. 2005; 25: 847-853.
• 65. Leung J., Jayachandran M., Kendall-Thomas J. i wsp.: Pilot study of sex differences in chemokine/cytokine markers of atherosclerosis in humans. Gend. Med. 2008; 5: 44-52.
• 66. Breland U.M., Halvorsen B., Hol J. i wsp.: A potential role of the CXC chemokine GROa in atherosclerosis and plaque destabilization: downregulatory effects of statins. Arterioscler. Thromb. Vasc. Biol. 2008; 28: 1005-1011.

• Document Type: article