Chemokines and thrombogenicity

Michele P. Lambert; Bruce S. Sachais; M. Anna Kowalska

doi:10.1160/TH07-01-0046

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(05): 722-729
DOI: 10.1160/TH07-01-0046

Theme Issue Article

Schattauer GmbH

Chemokines and thrombogenicity

Michele P. Lambert

¹Division of Hematology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

²Department of Pediatrics

,

Bruce S. Sachais

³Department of Pathology and Laboratory Medicine University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

,

M. Anna Kowalska

¹Division of Hematology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

⁴Center for Medical Biology, Polish Academy of Science, Lodz, Poland

› Author Affiliations

Abstract

Summary

Thrombosis is an important clinical entity, and pathologic thrombosis, in the form of atherosclerosis, is a major cause of morbidity and mortality. Recent research points to the role of chemokines, normally key factors in inflammation, in thrombogenesis. Many recent studies in murine transgenic and knockout models show that chemokines and their receptors are important modulators of the process of thrombus formation, particularly in atherosclerosis. Platelet-released chemokines can potentiate or inhibit thrombosis and inflammation.This review focuses on the role of chemokines in platelet activation and thrombosis, particularly as it relates to atherosclerosis. Further studies to define this complex interaction are underway.

Keywords

Chemokines - thrombosis - atherosclerosis - chemokine receptors - platelets

Full Text

References

References
1 Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity 2000; 12: 121-127.
2 Strieter RM, Burdick MD, Gomperts BN. et al. CXC chemokines in angiogenesis. Cytokine Growth Factor Rev 2005; 16: 593-609.
3 Holt JC, Rabellino EM, Gewirtz AM. et al. Occurrence of platelet basic protein, a precursor of low affinity platelet factor 4 and beta-thromboglobulin, in human platelets and megakaryocytes. Exp Hematol 1988; 16: 302-306.
4 Niewiarowski S, Thomas DP. Platelet factor 4 and adenosine diphosphate release during human platelet aggregation. Nature 1969; 222: 1269-1270.
5 Deuel TF, Keim PS, Farmer M. et al. Amino acid sequence of human platelet factor 4. Proc Natl Acad Sci USA 1977; 74: 2256-2258.
6 von Hundelshausen P, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ Res 2007; 100: 27-40.
7 Clemetson KJ, Clemetson JM, Proudfoot AE. et al. Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets. Blood 2000; 96: 4046-4054.
8 Humphries J, McGuinness CL, Smith A. et al. Monocyte chemotactic protein-1 (MCP-1) accelerates the organization and resolution of venous thrombi. J Vasc Surg 1999; 30: 894-899.
9 Frangogiannis NG, Entman ML. Targeting the chemokines in myocardial inflammation. Circulation 2004; 110: 1341-1342.
10 Schecter AD, Calderon TM, Berman AB. et al. Human vascular smooth muscle cells possess functional CCR5. J Biol Chem 2000; 275: 5466-5471.
11 Mause SF, von Hundelshausen P, Zernecke A. et al. Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol 2005; 25: 1512-1518.
12 Ma B, Zhu Z, Homer RJ. et al. The C10/CCL6 chemokine and CCR1 play critical roles in the pathogenesis of IL-13-induced inflammation and remodeling. J Immunol 2004; 172: 1872-1881.
13 Wang X, Li X, Yue TL. et al. Expression of monocyte chemotactic protein-3 mRNA in rat vascular smooth muscle cells and in carotid artery after balloon angioplasty. Biochim Biophys Acta 2000; 1500: 41-48.
14 Abi-Younes S, Si-Tahar M, Luster AD. The CC chemokines MDC and TARC induce platelet activation via CCR4. Thromb Res 2001; 101: 279-289.
15 Gear AR, Camerini D. Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation 2003; 10: 335-350.
16 Gear AR, Suttitanamongkol S, Viisoreanu D. et al. Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet function. Blood 2001; 97: 937-945.
17 Reape TJ, Rayner K, Manning CD. et al. Expression and cellular localization of the CC chemokines PARC and ELC in human atherosclerotic plaques. Am J Pathol 1999; 154: 365-374.
18 Zernecke A, Weber C. Inflammatory mediators in atherosclerotic vascular disease. Basic Res Cardiol 2005; 100: 93-101.
19 Kowalska MA, Ratajczak MZ, Majka M. et al. Stromal cell-derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets. Blood 2000; 96: 50-57.
20 Boisvert WA. Modulation of atherogenesis by chemokines. Trends Cardiovasc Med 2004; 14: 161-165.
21 Slungaard A, Key NS. Platelet factor 4 stimulates thrombomodulin protein C-activating cofactor activity. A structure-function analysis. J Biol Chem 1994; 269: 25549-25556.
22 Petersen F, Bock L, Flad HD, Brandt E.. Platelet factor 4-induced neutrophil-endothelial cell interaction: involvement of mechanisms and functional consequences different from those elicited by interleukin-8. Blood 1999; 94: 4020-4028.
23 Smith DF, Galkina E, Ley K. et al. GRO family chemokines are specialized for monocyte arrest from flow. Am J Physiol Heart Circ Physiol 2005; 289: H1976-1984.
24 Walz A, Baggiolini M. Generation of the neutrophil- activating peptide NAP-2 from platelet basic protein or connective tissue-activating peptide III through monocyte proteases. J Exp Med 1990; 171: 449-454.
25 Holt JC, Yan ZQ, Lu WQ. et al. Isolation, characterization, and immunological detection of neutrophil-activating peptide 2: a proteolytic degradation product of platelet basic protein. Proc Soc Exp Biol Med 1992; 199: 171-177.
26 Henke PK, Wakefield TW, Kadell AM. et al. Interleukin- 8 administration enhances venous thrombosis resolution in a rat model. J Surg Res 2001; 99: 84-91.
27 Kowalska MA, Ratajczak J, Hoxie J. et al. Megakaryocyte precursors, megakaryocytes and platelets express the HIV co-receptor CXCR4 on their surface: determination of response to stromal-derived factor-1 by megakaryocytes and platelets. Br J Haematol 1999; 104: 220-229.
28 Wang JF, Liu ZY, Groopman JE. The alpha-chemokine receptor CXCR4 is expressed on the megakaryocytic lineage from progenitor to platelets and modulates migration and adhesion. Blood 1998; 92: 756-764.
29 Oberlin E, Amara A, Bachelerie F. et al. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 1996; 382: 833-835.
30 Mohle R, Bautz F, Rafii S. et al. The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1. Blood 1998; 91: 4523-4530.
31 Imai T, Chantry D, Raport CJ. et al. Macrophagederived chemokine is a functional ligand for the CC chemokine receptor 4. J Biol Chem 1998; 273: 1764-1768.
32 Imai T, Baba M, Nishimura M. et al. The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4. J Biol Chem 1997; 272: 15036-15042.
33 Abi-Younes S, Sauty A, Mach F. et al. The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques. Circ Res 2000; 86: 131-138.
34 Shenkman B, Brill A, Brill G. et al. Differential response of platelets to chemokines: RANTES non-competitively inhibits stimulatory effect of SDF-1 alpha. J Thromb Haemost 2004; 02: 154-160.
35 Bazan JF, Bacon KB, Hardiman G. et al. A new class of membrane-bound chemokine with a CX3C motif. Nature 1997; 385: 640-644.
36 Schafer A, Schulz C, Eigenthaler M. et al. Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion. Blood 2004; 103: 407-412.
37 Holt JC, Niewiarowski S. Biochemistry of alpha granule proteins. Semin Hematol 1985; 22: 151-163.
38 Rucinski B, Niewiarowski S, James P. et al. Antiheparin proteins secreted by human platelets. purification, characterization, and radioimmunoassay. Blood 1979; 53: 47-62.
39 Zucker MB, Katz IR. Platelet factor 4: production, structure, and physiologic and immunologic action. Proc Soc Exp Biol Med 1991; 198: 693-702.
40 El-Gedaily A, Schoedon G, Schneemann M. et al. Constitutive and regulated expression of platelet basic protein in human monocytes. J Leukoc Biol 2004; 75: 495-503.
41 Schaffner A, Rhyn P, Schoedon G. et al. Regulated expression of platelet factor 4 in human monocytes-- role of PARs as a quantitatively important monocyte activation pathway. J Leukoc Biol 2005; 78: 202-209.
42 Brandt E, Ludwig A, Petersen F. et al. Platelet-derived CXC chemokines: old players in new games. Immunol Rev 2000; 177: 204-216.
43 Chesterman CN, McGready JR, Doyle DJ. et al. Plasma levels of platelet factor 4 measured by radioimmunoassay. Br J Haematol 1978; 40: 489-500.
44 Zhang C, Thornton MA, Kowalska MA. et al. Localization of distal regulatory domains in the megakaryocyte- specific platelet basic protein/platelet factor 4 gene locus. Blood 2001; 98: 610-617.
45 Fuckami M, Homsen H, Kowalksa M. et al. Platelet Secretion. In: Hemostasis and Thrombosis Basic Principles and Clinical Practice. Philadelphia: Lippincott, Williams & Wilkins; 2001: 561-573.
46 Eisman R, Surrey S, Ramachandran B. et al. Structural and functional comparison of the genes for human platelet factor 4 and PF4alt. Blood 1990; 76: 336-344.
47 Struyf S, Burdick MD, Proost P. et al. Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis. Circ Res 2004; 95: 855-857.
48 Holt JC, Harris ME, Holt AM. et al. Characterization of human platelet basic protein, a precursor form of low-affinity platelet factor 4 and beta-thromboglobulin. Biochemistry 1986; 25: 1988-1996.
49 Walz A, Dewald B, von Tscharner V. et al. Effects of the neutrophil-activating peptide NAP-2, platelet basic protein, connective tissue-activating peptide III and platelet factor 4 on human neutrophils. J Exp Med 1989; 170: 1745-1750.
50 Car BD, Baggiolini M, Walz A. Formation of neutrophil- activating peptide 2 from platelet-derived connective- tissue-activating peptide III by different tissue proteinases. Biochem J 1991; 275: 581-584.
51 Dewald B, Rindler-Ludwig R, Bretz U. et al. Subcellular localization and heterogeneity of neutral proteases in neutrophilic polymorphonuclear leukocytes. J Exp Med 1975; 141: 709-723.
52 Campbell EJ, Silverman EK, Campbell MA. Elastase and cathepsin G of human monocytes. Quantification of cellular content, release in response to stimuli, and heterogeneity in elastase-mediated proteolytic activity. J Immunol 1989; 143: 2961-2968.
53 Hope W, Martin TJ, Chesterman CN. et al. Human beta-thromboglobulin inhibits PGI2 production and binds to a specific site in bovine aortic endothelial cells. Nature 1979; 282: 210-212.
54 Carr ME, White GC 2nd, Gabriel DA. Platelet factor 4 enhances fibrin fiber polymerization. Thromb Res 1987; 45: 539-543.
55 Weisel JW, Nagaswami C. Computer modeling of fibrin polymerization kinetics correlated with electron microscope and turbidity observations: clot structure and assembly are kinetically controlled. Biophys J 1992; 63: 111-128.
56 Amelot AA, Tagzirt M, Ducouret G. et al. Platelet factor 4 (CXCL4) seals blood clots by altering the structure of fibrin. J Biol Chem 2007; 282: 710-720.
57 Marcum JA, McKenney JB, Rosenberg RD. Acceleration of thrombin-antithrombin complex formation in rat hindquarters via heparinlike molecules bound to the endothelium. J Clin Invest 1984; 74: 341-350.
58 Capitanio AM, Niewiarowski S, Rucinski B. et al. Interaction of platelet factor 4 with human platelets. Biochim Biophys Acta 1985; 839: 161-173.
59 Dudek AZ, Pennell CA, Decker TD. et al. Platelet factor 4 binds to glycanated forms of thrombomodulin and to protein C. A potential mechanism for enhancing generation of activated protein C. J Biol Chem 1997; 272: 31785-31792.
60 Slungaard A, Fernandez JA, Griffin JH. et al. Platelet factor 4 enhances generation of activated protein C in vitro and in vivo. Blood 2003; 102: 146-151.
61 Clark-Lewis I, Dewald B, Geiser T. et al. Platelet factor 4 binds to interleukin 8 receptors and activates neutrophils when its N terminus is modified with Glu- Leu-Arg. Proc Natl Acad Sci USA 1993; 90: 3574-3577.
62 Scheuerer B, Ernst M, Durrbaum-Landmann I. et al. The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages. Blood 2000; 95: 1158-1166.
63 Fricke I, Mitchell D, Petersen F. et al. Platelet factor 4 in conjunction with IL-4 directs differentiation of human monocytes into specialized antigen-presenting cells. Faseb J 2004; 18: 1588-1590.
64 Sachais BS, Higazi AA, Cines DB. et al. Interactions of platelet factor 4 with the vessel wall. Semin Thromb Hemost 2004; 30: 351-358.
65 Rao AK, Niewiarowski S, James P. et al. Effect of heparin on the in vivo release and clearance of human platelet factor 4. Blood 1983; 61: 1208-1214.
66 Lasagni L, Francalanci M, Annunziato F. et al. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med 2003; 197: 1537-1549.
67 Yu G, Rux AH, Ma P. et al. Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-kappaBdependent manner. Blood 2005; 105: 3545-3551.
68 Li ZQ, Liu W, Park KS. et al. Defining a second epitope for heparin-induced thrombocytopenia/thrombosis antibodies using KKO, a murine HIT-like monoclonal antibody. Blood 2002; 99: 1230-1236.
69 Locati M, Murphy PM. Chemokines and chemokine receptors: biology and clinical relevance in inflammation and AIDS. Annu Rev Med 1999; 50: 425-440.
70 Baggiolini M, Dewald B, Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol 1994; 55: 97-179.
71 Wuyts A, Proost P, Lenaerts JP. et al. Differential usage of the CXC chemokine receptors 1 and 2 by interleukin- 8, granulocyte chemotactic protein-2 and epithelial-cell-derived neutrophil attractant-78. Eur J Biochem 1998; 255: 67-73.
72 Lee J, Horuk R, Rice GC. et al. Characterization of two high affinity human interleukin-8 receptors. J Biol Chem 1992; 267: 16283-16287.
73 Bozic CR, Gerard NP, von Uexkull-Guldenband C. et al. The murine interleukin 8 type B receptor homologue and its ligands. Expression and biological characterization. J Biol Chem 1994; 269: 29355-29358.
74 Heinrich JN, Bravo R. N51 competes 125I-interleukin (IL)-8 binding to IL-8R beta but not IL-8R alpha. Structure-function analysis using N51/IL-8 chimeric molecules. J Biol Chem 1995; 270: 28014-28017.
75 Fan X, Patera AC, Pong-Kennedy A. et al. Murine CXCR1 is a functional receptor for GCP-2/CXCL6 AND IL-8/CXCL8. J Biol Chem. 2006 epub ahead of print
76 Eslin DE, Zhang C, Samuels KJ. et al. Transgenic mice studies demonstrate a role for platelet factor 4 in thrombosis: dissociation between anticoagulant and antithrombotic effect of heparin. Blood 2004; 104: 3173-3180.
77 Paredes N, Wang A, Berry LR. et al. Mechanisms responsible for catalysis of the inhibition of factor Xa or thrombin by antithrombin using a covalent antithrombin- heparin complex. J Biol Chem 2003; 278: 23398-23409.
78 Bernabei A, Gikakis N, Maione TE. et al. Reversal of heparin anticoagulation by recombinant platelet factor 4 and protamine sulfate in baboons during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1995; 109: 765-771.
79 Denton J, Lane DA, Thunberg L. et al. Binding of platelet factor 4 to heparin oligosaccharides. Biochem J 1983; 209: 455-460.
80 Shanberge JN, Quattrociocchi-Longe TM. Influence of platelet factor 4 on the neutralization of heparin by protamine. Ann NY Acad Sci 1989; 556: 354-365.
81 Henke PK, Pearce CG, Moaveni DM. et al. Targeted deletion of CCR2 impairs deep vein thombosis resolution in a mouse model. J Immunol 2006; 177: 3388-3397.
82 Boring L, Gosling J, Cleary M. et al. Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 1998; 394: 894-897.
83 Boisvert WA, Santiago R, Curtiss LK. et al. A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest 1998; 101: 353-363.
84 Veillard NR, Steffens S, Pelli G. et al. Differential influence of chemokine receptors CCR2 and CXCR3 in development of atherosclerosis in vivo. Circulation 2005; 112: 870-878.
85 Braunersreuther V, Zernecke A, Arnaud C. et al. Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2007; 27: 373-379.
86 Pitsilos S, Hunt J, Mohler ER. et al. Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parameters. Thromb Haemost 2003; 90: 1112-1120.
87 Sevitt S. Platelets and foam cells in the evolution of atherosclerosis. Histological and immunohistological studies of human lesions. Atherosclerosis 1986; 61: 107-115.
88 Chesterman CN, Berndt MC. Platelet and vessel wall interaction and the genesis of atherosclerosis. Clin Haematol 1986; 15: 323-353.
89 Davies MJ. The contribution of thrombosis to the clinical expression of coronary atherosclerosis. Thromb Res 1996; 82: 1-32.
90 Hawiger J. Mechanisms involved in platelet vessel wall interaction. Thromb Haemost 1995; 74: 369-372.
91 Holvoet P, Collen D. Thrombosis and atherosclerosis. Curr Opin Lipidol 1997; 08: 320-328.
92 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 801-809.
93 Fuhrman B, Brook GJ, Aviram M. Lipid-protein particles secreted from activated platelets reduce macrophage uptake of low density lipoprotein. Atherosclerosis 1991; 89: 163-173.
94 Kruth HS. Cholesterol accumulation in vascular smooth muscle cells incorporated into platelet-rich plasma clots. Lab Invest 1985; 53: 634-638.
95 Lutgens E, Gorelik L, Daemen MJ. et al. Requirement for CD154 in the progression of atherosclerosis. Nat Med 1999; 05: 1313-1316.
96 Henn V, Slupsky JR, Grafe M. et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-594.
97 von Hundelshausen P, Koenen RR, Sack M. et al. Heterophilic interactions of platelet factor 4 and RANTES promote monocyte arrest on endothelium. Blood 2005; 105: 924-930.
98 Frenette PS, Johnson RC, Hynes RO. et al. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci USA 1995; 92: 7450-7454.
99 Johnson RC, Chapman SM, Dong ZM. et al. Absence of P-selectin delays fatty streak formation in mice. J Clin Invest 1997; 99: 1037-1043.
100 Burger PC, Wagner DD. Platelet P-selectin facilitates atherosclerotic lesion development. Blood 2003; 101: 2661-2666.
101 Collins RG, Velji R, Guevara NV. et al. P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. J Exp Med 2000; 191: 189-194.
102 Manka D, Collins RG, Ley K. et al. Absence of p-selectin, but not intercellular adhesion molecule-1, attenuates neointimal growth after arterial injury in apolipoprotein e-deficient mice. Circulation 2001; 103: 1000-1005.
103 Massberg S, Brand K, Gruner S. et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 2002; 196: 887-896.
104 Huo Y, Schober A, Forlow SB. et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med 2003; 09: 61-67.
105 Huo Y, Ley KF. Role of platelets in the development of atherosclerosis. Trends Cardiovasc Med 2004; 14: 18-22.
106 Schober A, Manka D, von Hundelshausen P. et al. Deposition of platelet RANTES triggering monocyte recruitment requires P-selectin and is involved in neointima formation after arterial injury. Circulation 2002; 106: 1523-1529.
107 Nassar T, Sachais BS, Akkawi S. et al. Platelet factor 4 enhances the binding of oxidized low-density lipoprotein to vascular wall cells. J Biol Chem 2003; 278: 6187-6193.
108 Sachais BS, Kuo A, Nassar T. et al. Platelet factor 4 binds to low-density lipoprotein receptors and disrupts the endocytic machinery, resulting in retention of low-density lipoprotein on the cell surface. Blood 2002; 99: 3613-3622.
109 Nelken NA, Coughlin SR, Gordon D. et al. Monocyte chemoattractant protein-1 in human atheromatous plaques. J Clin Invest 1991; 88: 1121-1127.
110 Yla-Herttuala S, Lipton BA, Rosenfeld ME. et al. Macrophages and smooth muscle cells express lipoprotein lipase in human and rabbit atherosclerotic lesions. Proc Natl Acad Sci USA 1991; 88: 10143-10147.
111 Huo Y, Weber C, Forlow SB. et al. The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium. J Clin Invest 2001; 108: 1307-1314.
112 Wilcox JN, Nelken NA, Coughlin SR. et al. Local expression of inflammatory cytokines in human atherosclerotic plaques. J Atheroscler Thromb 1994; 01 (Suppl. 01) (Suppl) S10-13.
113 Herder C, Baumert J, Thorand B. et al. Chemokines and incident coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Arterioscler Thromb Vasc Biol 2006; 26: 2147-2152.
114 McDermott DH, Halcox JP, Schenke WH. et al. Association between polymorphism in the chemokine receptor CX3CR1 and coronary vascular endothelial dysfunction and atherosclerosis. Circ Res 2001; 89: 401-407.