Right on the spot

Carlo Laudanna; Ronen Alon

doi:10.1160/TH05-07-0482

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2006; 95(01): 5-11
DOI: 10.1160/TH05-07-0482

Theme Issue Article

Schattauer GmbH

Right on the spot

Chemokine triggering of integrin–mediated arrest of rolling leukocytes

Carlo Laudanna

¹Department of Pathology, University of Verona, Verona, Italy

,

Ronen Alon

²Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

› Institutsangaben

Abstract

Summary

The arrest of rolling leukocytes on various target vascular beds is crucial for their recruitment at inflammatory sites and secondary lymphoid tissues. Leukocyte arrest is predominantly mediated by integrins interacting with either constitutive or inducible endothelial ligands. Integrins are cytoskeletally regulated heterodimers maintained in largely low affinity conformational states on circulating leukocytes. For arrest to occur, the affinity of integrin heterodimers must be enhanced in situ upon leukocyte encounter with proper endothelial-displayed chemokines or chemoattractants which bind and signal through specific G-protein coupled receptors (GPCRs) on the leukocyte surface. Recent studies suggest that this integrin activation involves rapid conformational alterations locally induced at confined leukocyte-endothelial contact sites. Following binding, integrin microclustering reinforced by associations with the cortical actin cytoskeleton further enhances integrin-mediated adhesiveness under shear stress. These events are controlled by complex signaling events, involving a series of small GTPases, as well as protein and lipid kinases which are triggered by chemokine bound GPCRs. To rapidly mediate this specialized function, subsets of signaling proteins and their specific targets are thought to preexist in pre-assembled multi-molecular complexes or signalosomes. Recent in vitro dissection of chemokine-triggered integrin activation on lymphocytes and neutrophils suggests that these signalosomes may vary both in composition and mode of activity between different immune cell types and distinct integrins. We review in this article recent findings on key elements implicated in chemokine triggering of integrin activation on rolling leukocytes, and discuss the possible existence of preformed proadhesive signaling networks in different subsets of leukocytes.

Keywords

Integrins - chemokines - selectins - leukocytes - signal transduction - inflammation

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References
1 Butcher EC. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 1991; 67: 1033-6.
2 Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 1994; 76: 301-14.
3 von Andrian UH, Mackay CR. T-cell function and migration. Two sides of the same coin. N Engl J Med 2000; 343: 1020-34.
4 Ley K. Pathways and bottlenecks in the web of inflammatory adhesion molecules and chemoattractants. Immunol Res 2001; 24: 87-95.
5 Kubes P. Introduction: The complexities of leukocyte recruitment. Semin Immunol 2002; 14: 65-72.
6 del Pozo MA, Nieto M, Serrador JM. et al. The two poles of the lymphocyte: specialized cell compartments for migration and recruitment. Cell Adhes Commun 1998; 06: 125-33.
7 Alon R, Grabovsky V, Feigelson S. Chemokine induction of integrin adhesiveness on rolling and arrested leukocytes: local signaling events or global stepwise activation?. Microcirculation 2003; 10: 297-311.
8 Constantin G, Majeed M, Giagulli C. et al. Chemokines trigger immediate β2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under flow. Immunity 2000; 13: 759-69.
9 Shamri R, Grabovsky V, Gauguet JM. et al. Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endotheliumbound chemokines. Nat Immunol 2005; 06: 497-506.
10 Giagulli C, Scarpini E, Ottoboni L. et al. RhoA and zeta PKC control distinct modalities of LFA-1 activation by chemokines. Critical role of LFA-1 affinity triggering in lymphocyte in vivo homing. Immunity 2004; 20: 25-35.
11 Carman CV, Springer TA. Integrin avidity regulation: are changes in affinity and conformation underemphasized?. Curr Opin Cell Biol 2003; 15: 547-56.
12 Shimaoka M, Xiao T, Liu JH. et al. Structures of the αL I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation. Cell 2003; 112: 99-111.
13 Salas A, Shimaoka M, Kogan AN. et al. Rolling adhesion through an extended conformation of integrin αLβ2 and relation to αI and βI-like domain interaction. Immunity 2004; 20: 393-406.
14 Peled A, Grabovsky V, Habler L. et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34+ cells on vascular endothelium under shear flow. J Clin Invest 1999; 104: 1199-211.
15 Grabovsky V, Feigelson S, Chen C. et al. Subsecond induction of α4 integrin clustering by immobilized chemokines enhances leukocyte capture and rolling under flow prior to firm adhesion to endothelium. J Exp Med 2000; 192: 495-505.
16 Grabovsky V, Dwir O, Alon R. Endothelial chemokines destabilize L-selectin-mediated lymphocyte rolling without inducing selectin shedding. J Biol Chem 2002; 277: 20640-50.
17 Fong AM, Robinson LA, Steeber DA. et al. Fractalkine and CX3CR1 mediatea novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow. J Exp Med 1998; 188: 1413-9.
18 Campbell JJ, Hedrick J, Zlotnik A. et al. Chemokines and the arrest of lymphocytes rolling under flow conditions. Science 1998; 279: 381-4.
19 D’Ambrosio D, Lecca P, Constantin G. et al. Concurrency in leukocyte vascular recognition: developing the tools for a predictive computer model. Trends Immunol 2004; 25: 411-6.
20 D’Ambrosio D, Albanesi C, Lang R. et al. Quantitative differences in chemokine receptor engagement generate diversity in integrin-dependent lymphocyte adhesion. J Immunol 2002; 169: 2303-12.
21 Abitorabi MA, Pachynski RK, Ferrando RE. et al. Presentation of integrins on leukocyte microvilli: a role for the extracellular domain in determining membrane localization. J Cell Biol 1997; 139: 563-71.
22 Chan JR, Hyduk SJ, Cybulsky MI. Chemoattractants induce a rapid and transient upregulation of monocyte α4 integrin affinity for vascular cell adhesion molecule1 which mediates arrest: an early step in the process of emigration. J Exp Med 2001; 193: 1149-58.
23 Franitza S, Grabovsky V, Wald O. et al. Differential usage of VLA-4 and CXCR4 by CD3+CD56+ NKT cells and CD56+CD16+ NK cells regulates their interaction with endothelial cells. Eur J Immunol 2004; 34: 1333-41.
24 Weber C, Springer TA. Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbβ3 and stimulated by platelet-activating factor. J Clin Invest 1997; 100: 2085-93.
25 von Hundelshausen P, Weber KS, Huo Y. et al. RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation 2001; 103: 1772-7.
26 Huo Y, Schober A, Forlow SB. et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med 2003; 09: 61-7.
27 Smith ML, Olson TS, Ley K. CXCR2- and E-selectin-induced neutrophil arrest during inflammation in vivo . J Exp Med 2004; 200: 935-9.
28 Kim M, Carman CV, Yang W. et al. The primacy of affinity over clustering in regulation of adhesiveness of the integrin αLβ2. J Cell Biol 2004; 167: 1241-53.
29 Laudanna C, Kim JY, Constantin G. et al. Rapid leukocyte integrin activation by chemokines. Immunol Rev 2002; 186: 37-46.
30 Laudanna C, Campbell JJ, Butcher EC. Role of Rho in chemoattractant-activated leukocyte adhesion through integrins. Science 1996; 271: 981-3.
31 Cherry LK, Li X, Schwab P. et al. RhoH is required to maintain the integrin LFA-1 in a nonadhesive state on lymphocytes. Nat Immunol 2004; 05: 961-7.
32 Katagiri K, Maeda A, Shimonaka M. et al. RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nat Immunol 2003; 04: 741-8.
33 Shimonaka M, Katagiri K, Nakayama T. et al. Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow. J Cell Biol 2003; 161: 417-27.
34 Katagiri K, Ohnishi N, Kabashima K. et al. Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking. Nat Immunol 2004; 05: 1045-51.
35 Kinashi T, Katagiri K. Regulation of lymphocyte adhesion and migration by the small GTPase Rap1 and its effector molecule, RAPL. Immunol Lett 2004; 93: 1-5.
36 Alon R, Etzioni A. LAD-III, a novel group of leukocyte integrin activation deficiencies. Trends Immunol 2003; 24: 561-6.
37 Kinashi T, Aker M, Sokolovsky-Eisenberg M. et al. LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bonds. Blood 2004; 103: 1033-6.
38 Nombela-Arrieta C, Lacalle RA, Montoya MC. et al. Differential requirements for DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing. Immunity 2004; 21: 429-41.
39 Laudanna C, Mochly-Rosen D, Liron T. et al. Evidence of zeta protein kinase C involvement in polymorphonuclear neutrophil integrin-dependent adhesion and chemotaxis. J Biol Chem 1998; 273: 30306-15.
40 Kolanus W, Nagel W, Schiller B. et al. Alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule. Cell 1996; 86: 233-42.
41 Geiger C, Nagel W, Boehm T. et al. Cytohesin-1 regulates beta-2 integrin-mediated adhesion through both ARF-GEF function and interaction with LFA-1. EMBO J 2000; 19: 2525-36.
42 Weber KS, Weber C, Ostermann G. et al. Cytohesin-1 is a dynamic regulator of distinct LFA-1 functions in leukocyte arrest and transmigration triggered by chemokines. Curr Biol 2001; 11: 1969-74.
43 Garcia-Bernal D, Wright N, Sotillo-Mallo E. et al. Vav1 and Rac control chemokine-promoted T lymphocyte adhesion mediated by the integrin alpha4beta1. Mol Biol Cell 2005; 16: 3223-35.
44 Luscinskas FW, Ma S, Nusrat A. et al. Leukocyte transendothelial migration: A junctional affair. Semin Immunol 2002; 14: 105-13.
45 Schenkel AR, Mamdouh Z, Muller WA. Locomotion of monocytes on endothelium is a critical step during extravasation. Nat Immunol 2004; 05: 393-400.
46 Laudanna C, Campbell JJ, Butcher EC. Elevation of intracellular cAMP inhibits RhoA activation and integrin-dependent leukocyte adhesion induced by chemoattractants. J Biol Chem 1997; 272: 24141-4.
47 Hughes PE, Renshaw MW, Pfaff M. et al. Suppression of integrin activation: a novel function of a Ras/ Raf-initiated MAP kinase pathway. Cell 1997; 88: 521-30.
48 Weber KS, Ostermann G, Zernecke A. et al. Dual role of h-ras in regulation of lymphocyte function antigen-1 activity by stromal cell-derived factor-1alpha: implications for leukocyte transmigration. Mol Biol Cell 2001; 12: 3074-86.
49 Friedrich EB, Sinha S, Li L. et al. Role of integrinlinked kinase in leukocyte recruitment. J Biol Chem 2002; 277: 16371-5.
50 Campbell ID, Ginsberg MH. The talin-tail interaction places integrin activation on FERM ground. Trends Biochem Sci 2004; 29: 429-35.
51 Manes S, Lacalle RA, Gomez-Mouton C. et al. Membrane raft microdomains in chemokine receptor function. Semin Immunol 2001; 13: 147-57.
52 Shamri R, Grabovsky V, Feigelson S. et al. Chemokine-stimulation of lymphocyte α4 integrin avidity but not of LFA-1 avidity to endothelial ligands under shear flow requires cholesterol membrane rafts. J Biol Chem 2002; 277: 40027-35.
53 Weber C, Weber KS, Klier C. et al. Specialized roles of the chemokine receptors CCR1 and CCR5 in the recruitment of monocytes and Th1-like/CD45RO+ T cells. Blood 2001; 97: 1144-6.
54 Ley K. Arrest chemokines. Microcirculation 2003; 10: 289-95.
55 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: 700-12.
56 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: 1307-14.
57 Amatruda 3rd TT, Gerard NP, Gerard C. et al. Specific interactions of chemoattractant factor receptors with G-proteins. J Biol Chem 1993; 268: 10139-44.
58 Arai H, Charo IF. Differential regulation of G-protein-mediated signaling by chemokine receptors. J Biol Chem 1996; 271: 21814-9.
59 Kuang Y, Wu Y, Jiang H. et al. Selective G protein coupling by C-C chemokine receptors. J Biol Chem 1996; 271: 3975-8.
60 Haribabu B, Zhelev DV, Pridgen BC. et al. Chemoattractant receptors activate distinct pathways for chemotaxis and secretion. Role of G-protein usage. J Biol Chem 1999; 274: 37087-92.
61 Loike JD, Cao L, Budhu S. et al. Differential regulation of β1 integrins by chemoattractants regulates neutrophil migration through fibrin. J Cell Biol 1999; 144: 1047-56.
62 Rabin RL, Park MK, Liao F. et al. Chemokine receptor responses on T cells are achieved through regulation of both receptor expression and signaling. J Immunol 1999; 162: 3840-50.
63 Mellado M, Rodriguez-Frade JM, Vila-Coro AJ. et al. Chemokine receptor homo-or heterodimerization activates distinct signaling pathways. EMBO J 2001; 20: 2497-507.
64 Singer II, Scott S, Kawka DW. et al. CCR5, CXCR4, and CD4 are clustered and closely apposed on microvilli of human macrophages and T cells. J Virol 2001; 75: 3779-90.
65 Berlin C, Bargatze RF, Campbell JJ. et al. α4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 1995; 80: 413-22.
66 Moore KL, Patel KD, Bruehl RE. et al. P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin. J Cell Biol 1995; 128: 661-671.
67 von Andrian UH, Hasslen SR, Nelson RD. et al. A central role for microvillous receptor presentation in leukocyte adhesion under flow. Cell 1995; 82: 989-99.
68 Hartwell LH, Hopfield JJ, Leibler S. et al. From molecular to modular cell biology. Nature 1999; 402 (6761 Suppl) C47-52.
69 Ravasz E, Somera AL, Mongru DA. et al Hierarchical organization of modularity in metabolic networks. Science 2002; 297: 1551-5.
70 Rives AW, Galitski T. Modular organization of cellular networks. Proc Natl Acad Sci USA 2003; 100: 1128-33.