Thromb Haemost 2007; 97(05): 688-693
DOI: 10.1160/TH07-02-0105
Theme Issue Article
Schattauer GmbH

Chemokines at large: In-vivo mechanisms of their transport, presentation and clearance

Ian G. Colditz
1   CSIRO Livestock Industries, Armidale, New South Wales, Australia
,
Martin A. Schneider
2   Novartis Institutes of Biomedical Research, Vienna, Austria
,
Monika Pruenster
2   Novartis Institutes of Biomedical Research, Vienna, Austria
,
Antal Rot
2   Novartis Institutes of Biomedical Research, Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received 09 February 2007

Accepted after revision 02 March 2007

Publication Date:
24 November 2017 (online)

Summary

Compelling evidence implicates chemokines in the induction of leukocyte emigration from blood into tissues.This arguably most fundamental effect of chemokines is accomplished by triggering cognate classical G-protein-coupled chemokine receptors on the leukocyte surface. In vitro, these same receptors mediate leukocyte migration; however, the mechanisms of chemokine-induced migration differ between in-vivo and in-vitro settings. Leukocyte egress from blood is greatly influenced by haemodynamic conditions and requires full cooperation of endothelial cells.The behaviour of chemokines in their“native habitat” in vivo is controlled by their interaction with several accessory molecules which influence immobilisation, transport, clearance and degradation of chemokines and thereby determine the sites and duration of their action. Here we discuss peculiarities of the invivo actions of chemokines,the mechanisms of chemokine interaction with receptors and auxiliary molecules including interceptors, glycosaminoglycans and enzymes and illustrate how these interactions influence the outcome of chemokine activities in vivo.

 
  • References

  • 1 Metchnikoff E.. Lectures on the comparative pathology of inflammation. London: 1893
  • 2 Pfeffer W. Locomotorische Richtungsbewegungen durch chemische Reize. Untersuchungen aus dem Botanischen Institut Tübingen 1884; 01: 363-482.
  • 3 Clark ER. Observations on changes in blood vascular endothelium in the living animal. Am J Anat 1935; 57: 385-438.
  • 4 Butcher EC. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 1991; 67: 1033-1036.
  • 5 Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994; 76: 301-314.
  • 6 Luster AD, Alon R, and von Andrian UH. Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol 2005; 06: 1182-1190.
  • 7 Rot A, von Andrian UH. Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu Rev Immunol 2004; 22: 891-928.
  • 8 Cinamon G, Grabovsky V, Winter E. et al. Novel chemokine functions in lymphocyte migration through vascular endothelium under shear flow. J Leukoc Biol 2001; 69: 860-866.
  • 9 Cinamon G, Shinder V, Alon R. Shear forces promote lymphocyte migration across vascular endothelium bearing apical chemokines. Nat Immunol 2001; 02: 515-522.
  • 10 Cuvelier SL, Patel KD. Shear-dependent eosinophil transmigration on interleukin 4-stimulated endothelial cells: a role for endothelium-associated eotaxin-3. J Exp Med 2001; 194: 1699-1709.
  • 11 Schreiber T, Shinder V, Cain D. et al. Shear flow-dependent integration of apical and subendothelial chemokines in T cell transmigration: implications for locomotion and the multi-step paradigm. Blood 2007; 109: 1381-1386.
  • 12 Colditz IG. Margination and emigration of leucocytes. Surv Synth Pathol Res 1985; 04: 44-68.
  • 13 Doerschuk CM. Leukocyte trafficking in alveoli and airway passages. Respir Res 2000; 01: 136-140.
  • 14 Jongstra-Bilen J, Haidari M, Zhu SN. et al. Lowgrade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J Exp Med 2006; 203: 2073-2083.
  • 15 Colditz IG, Zwahlen RD, Baggiolini M. Neutrophil accumulation and plasma leakage induced in vivo by neutrophil-activating peptide-1. J Leukoc Biol 1990; 48: 129-137.
  • 16 Lira SA, Zalamea P, Heinrich JN. et al. Expression of the chemokine N51/KC in the thymus and epidermis of transgenic mice results in marked infiltration of a single class of inflammatory cells. J Exp Med 1994; 180: 2039-2048.
  • 17 Lira SA. Genetic approaches to study chemokine function. J Leukoc Biol 1996; 59: 45-52.
  • 18 Rot A. Chemotactic potency of recombinant human neutrophil attractant/activation protein-1 (interleukin- 8) for polymorphonuclear leukocytes of different species. Cytokine 1991; 03: 21-27.
  • 19 Alam R, Kumar D, Anderson-Walters D. et al. Macrophage inflammatory protein-1 alpha and monocyte chemoattractant peptide-1 elicit immediate and late cutaneous reactions and activate murine mast cells in vivo. J Immunol 1994; 152: 1298-1303.
  • 20 Hub E, Rot A. Binding of RANTES, MCP-1, MCP-3, and MIP-1alpha to cells in human skin. Am J Pathol 1998; 152: 749-757.
  • 21 Rot A. Binding of neutrophil attractant/activation protein-1 (interleukin 8) to resident dermal cells. Cytokine 1992; 04: 347-352.
  • 22 Das AM, Flower RJ, and Perretti M. Resident mast cells are important for eotaxin-induced eosinophil accumulation in vivo. J Leukoc Biol 1998; 64: 156-162.
  • 23 Ramos CD, Canetti C, Souto JT. et al. MIP- 1alpha[CCL3] acting on the CCR1 receptor mediates neutrophil migration in immune inflammation via sequential release of TNF-alpha and LTB4. J Leukoc Biol 2005; 78: 167-177.
  • 24 Wang Y, Thorlacius H. Mast cell-derived tumour necrosis factor-alpha mediates macrophage inflammatory protein-2-induced recruitment of neutrophils in mice. Br J Pharmacol 2005; 145: 1062-1068.
  • 25 Johnson-Leger C, Imhof BA. Forging the endothelium during inflammation: pushing at a half-open door?. Cell Tissue Res 2003; 314: 93-105.
  • 26 Callahan MK, Ransohoff RM. Analysis of leukocyte extravasation across the blood-brain barrier: conceptual and technical aspects. Curr Allergy Asthma Rep 2004; 04: 65-73.
  • 27 Engelhardt B, Wolburg H. Mini-review: Transendothelial migration of leukocytes: through the front door or around the side of the house?. Eur J Immunol 2004; 34: 2955-2963.
  • 28 Hordijk PL. Endothelial signalling events during leukocyte transmigration. Febs J 2006; 273: 4408-4415.
  • 29 Rot A. Endothelial cell binding of NAP-1/IL-8: role in neutrophil emigration. Immunol Today 1992; 13: 291-294.
  • 30 Middleton J, Neil S, Wintle J. et al. Transcytosis and surface presentation of IL-8 by venular endothelial cells. Cell 1997; 91: 385-395.
  • 31 Ley K. Integration of inflammatory signals by rolling neutrophils. Immunol Rev 2002; 186: 8-18.
  • 32 Campbell JJ, Hedrick J, Zlotnik A. et al. Chemokines and the arrest of lymphocytes rolling under flow conditions. Science 1998; 279: 381-384.
  • 33 Chan JR, Hyduk SJ, and Cybulsky MI. Chemoattractants induce a rapid and transient upregulation of monocyte alpha4 integrin affinity for vascular cell adhesion molecule 1 which mediates arrest: an early step in the process of emigration. J Exp Med 2001; 193: 1149-1158.
  • 34 Constantin G, Majeed M, Giagulli C. et al. Chemokines trigger immediate beta2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under flow. Immunity 2000; 13: 759-769.
  • 35 Kohrgruber N, Groger M, Meraner P. et al. Plasmacytoid dendritic cell recruitment by immobilized CXCR3 ligands. J Immunol 2004; 173: 6592-6602.
  • 36 Weber KS, von Hundelshausen P, Clark-Lewis I. et al. Differential immobilization and hierarchical involvement of chemokines in monocyte arrest and transmigration on inflamed endothelium in shear flow. Eur J Immunol 1999; 29: 700-712.
  • 37 Weber C, Weber KS, Klier C. et al. Specialized roles of the chemokine receptors CCR1 and CCR5 in the recruitment of monocytes and T(H)1-like/ CD45RO(+) T cells. Blood 2001; 97: 1144-1146.
  • 38 Hechtman DH, Cybulsky MI, Fuchs HJ. et al. Intravascular IL-8. Inhibitor of polymorphonuclear leukocyte accumulation at sites of acute inflammation. J Immunol 1991; 147: 883-892.
  • 39 Luscinskas FW, Kiely JM, Ding H. et al. In vitro inhibitory effect of IL-8 and other chemoattractants on neutrophil-endothelial adhesive interactions. J Immunol 1992; 149: 2163-2171.
  • 40 Martin C, Burdon PC, Bridger G. et al. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity 2003; 19: 583-593.
  • 41 Serbina NV, Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 2006; 07: 311-317.
  • 42 Tanaka Y, Adams DH, Hubscher S. et al. T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1 beta. Nature 1993; 361: 79-82.
  • 43 Webb LM, Ehrengruber MU, Clark-Lewis I. et al. Binding to heparan sulfate or heparin enhances neutrophil responses to interleukin 8. Proc Natl Acad Sci USA 1993; 90: 7158-7162.
  • 44 Ludwig A, Weber C. Transmembrane chemokines: Versatile 'special agents' in vascular inflammation. Thromb Haemost 2007; 694-703.
  • 45 Proudfoot AE, Handel TM, Johnson Z. et al. Glycosaminoglycan binding and oligomerization are essential for the in vivo activity of certain chemokines. Proc Natl Acad Sci USA 2003; 100: 1885-1890.
  • 46 Wang L, Fuster M, Sriramarao P. et al. Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine- mediated neutrophil trafficking during inflammatory responses. Nat Immunol 2005; 06: 902-910.
  • 47 Baekkevold ES, Yamanaka T, Palframan RT. et al. The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment. J Exp Med 2001; 193: 1105-1112.
  • 48 Nibbs R, Graham G, and Rot A. Chemokines on the move: control by the chemokine „interceptors“ Duffy blood group antigen and D6. Semin Immunol 2003; 15: 287-294.
  • 49 Pruenster M, Rot A. Throwing light on DARC. Biochem Soc Trans 2006; 34: 1005-1008.
  • 50 Rot A. Contribution of Duffy antigen to chemokine function. Cytokine Growth Factor Rev 2005; 16: 687-694.
  • 51 Hadley TJ, Peiper SC. From malaria to chemokine receptor: the emerging physiologic role of the Duffy blood group antigen. Blood 1997; 89: 3077-3091.
  • 52 Hadley TJ, Lu ZH, Wasniowska K. et al. Postcapillary venule endothelial cells in kidney express a multispecific chemokine receptor that is structurally and functionally identical to the erythroid isoform, which is the Duffy blood group antigen. J Clin Invest 1994; 94: 985-991.
  • 53 Horuk R, Martin AW, Wang Z. et al. Expression of chemokine receptors by subsets of neurons in the central nervous system. J Immunol 1997; 158: 2882-2890.
  • 54 Tournamille C, Colin Y, Cartron JP. et al. Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nat Genet 1995; 10: 224-228.
  • 55 Miller LH, Mason SJ, Dvorak JA. et al. Erythrocyte receptors for ( Plasmodium knowlesi) malaria: Duffy blood group determinants. Science 1975; 189: 561-563.
  • 56 Peiper SC, Wang ZX, Neote K. et al. The Duffy antigen/receptor for chemokines (DARC) is expressed in endothelial cells of Duffy negative individuals who lack the erythrocyte receptor. J Exp Med 1995; 181: 1311-1317.
  • 57 Lee JS, Frevert CW, Wurfel MM. et al. Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo. J Immunol 2003; 170: 5244-5251.
  • 58 Bruhl H, Vielhauer V, Weiss M. et al. Expression of DARC, CXCR3 and CCR5 in giant cell arteritis. Rheumatology (Oxford) 2005; 44: 309-313.
  • 59 Gardner L, Wilson C, Patterson AM. et al. Temporal expression pattern of Duffy antigen in rheumatoid arthritis: up-regulation in early disease. Arthritis Rheum 2006; 54: 2022-2026.
  • 60 Lee JS, Frevert CW, Thorning DR. et al. Enhanced expression of Duffy antigen in the lungs during suppurative pneumonia. J Histochem Cytochem 2003; 51: 159-166.
  • 61 Liu XH, Hadley TJ, Xu L. et al. Up-regulation of Duffy antigen receptor expression in children with renal disease. Kidney Int 1999; 55: 1491-1500.
  • 62 Patterson AM, Siddall H, Chamberlain G. et al. Expression of the duffy antigen/receptor for chemokines (DARC) by the inflamed synovial endothelium. J Pathol 2002; 197: 108-116.
  • 63 Segerer S, Regele H, Mac KM. et al. The Duffy antigen receptor for chemokines is up-regulated during acute renal transplant rejection and crescentic glomerulonephritis. Kidney Int 2000; 58: 1546-1556.
  • 64 Guyton AC, Granger HJ, and Taylor AE. Interstitial fluid pressure. Physiol Rev 1971; 51: 527-563.
  • 65 Gretz JE, Norbury CC, Anderson AO. et al. Lymphborne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. J Exp Med 2000; 192: 1425-1440.
  • 66 Palframan RT, Jung S, Cheng G. et al. Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues. J Exp Med 2001; 194: 1361-1373.
  • 67 Stein JV, Rot A, Luo Y. et al. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules. J Exp Med 2000; 191: 61-76.
  • 68 Nibbs RJ, Wylie SM, Yang J. et al. Cloning and characterization of a novel promiscuous human betachemokine receptor D6. J Biol Chem 1997; 272: 32078-32083.
  • 69 Nibbs RJ, Kriehuber E, Ponath PD. et al. The betachemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors. Am J Pathol 2001; 158: 867-877.
  • 70 Fra AM, Locati M, Otero K. et al. Cutting edge: scavenging of inflammatory CC chemokines by the promiscuous putatively silent chemokine receptor D6. J Immunol 2003; 170: 2279-2282.
  • 71 Mantovani A, Bonecchi R, Locati M. Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nat Rev Immunol 2006; 06: 907-918.
  • 72 Weber M, Blair E, Simpson CV. et al. The chemokine receptor D6 constitutively traffics to and from the cell surface to internalize and degrade chemokines. Mol Biol Cell 2004; 15: 2492-2508.
  • 73 Jamieson T, Cook DN, Nibbs RJ. et al. The chemokine receptor D6 limits the inflammatory response in vivo. Nat Immunol 2005; 06: 403-411.
  • 74 Graham GJ, McKimmie CS. Chemokine scavenging by D6: a movable feast?. Trends Immunol 2006; 27: 381-386.
  • 75 Ariel A, Fredman G, Sun YP. et al. Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Nat Immunol 2006; 07: 1209-1216.
  • 76 D'Amico G, Frascaroli G, Bianchi G. et al. Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys. Nat Immunol 2000; 01: 387-391.
  • 77 Dar A, Goichberg P, Shinder V. et al. Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nat Immunol 2005; 06: 1038-1046.
  • 78 Proost P, Struyf S, Van Damme J. Natural posttranslational modifications of chemokines. Biochem Soc Trans 2006; 34: 997-1001.
  • 79 Struyf S, Proost P, Van Damme J. Regulation of the immune response by the interaction of chemokines and proteases. Adv Immunol 2003; 81: 1-44.
  • 80 de Beaufort AJ, Pelikan DM, Elferink JG. et al. Effect of interleukin 8 in meconium on in-vitro neutrophil chemotaxis. Lancet 1998; 352: 102-105.
  • 81 Ohtsuki K, Hayase M, Akashi K. et al. Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions: an autoradiographic study. Circulation 2001; 104: 203-208.
  • 82 Rao WH, Evans GS, Finn A. The significance of interleukin 8 in urine. Arch Dis Child 2001; 85: 256-262.
  • 83 Rucinski B, Knight LC, Niewiarowski S. Clearance of human platelet factor 4 by liver and kidney: its alteration by heparin. Am J Physiol 1986; 251: H800-H807.
  • 84 Stiemer B, Buschmann A, Bisson S. et al. Interleukin- 8 in urine: a new diagnostic parameter for intra-amniotic infection after premature rupture of the membranes. Br J Obstet Gynaecol 1997; 104: 499-502.
  • 85 Darbonne WC, Rice GC, Mohler MA. et al. Red blood cells are a sink for interleukin 8, a leukocyte chemotaxin. J Clin Invest 1991; 88: 1362-1369.
  • 86 Dawson TC, Lentsch AB, Wang Z. et al. Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for chemokines (DARC). Blood 2000; 96: 1681-1684.
  • 87 Horuk R, Chitnis CE, Darbonne WC. et al. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Science 1993; 261: 1182-1184.
  • 88 Neote K, Darbonne W, Ogez J. et al. Identification of a promiscuous inflammatory peptide receptor on the surface of red blood cells. J Biol Chem 1993; 268: 12247-12249.
  • 89 Fukuma N, Akimitsu N, Hamamoto H. et al. A role of the Duffy antigen for the maintenance of plasma chemokine concentrations. Biochem Biophys Res Commun 2003; 303: 137-139.
  • 90 Lee JS, Wurfel MM, Matute-Bello G. et al. The Duffy Antigen Modifies Systemic and Local Tissue Chemokine Responses following Lipopolysaccharide Stimulation. J Immunol 2006; 177: 8086-8094.
  • 91 Jones AP, Webb LM, Anderson AO. et al. Normal human sweat contains interleukin-8. J Leukoc Biol 1995; 57: 434-437.
  • 92 Michie CA, Tantscher E, Schall T. et al. Physiological secretion of chemokines in human breast milk. Eur Cytokine Netw 1998; 09: 123-129.
  • 93 Rot A, Jones AP, Webb LM. Some aspects of NAP- 1/IL-8 pathophysiology. II: Chemokine secretion by exocrine glands. Adv Exp Med Biol 1993; 351: 77-85.