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DOI: 10.1160/TH08-11-0720
Neutrophils launch monocyte extravasation by release of granule proteins
Financial support: This work was supported by grants from the Deutsche Forschungsgemeinschaft (FOR809, SO876/1–1 to O.S., WE1913/7–2 and 10–1 to C.W., ZE827/1–1 to A.Z.) the Interdisciplinary Centre for Clinical Research “BIOMAT” within the Faculty of Medicine at the RWTH Aachen University (VV-B112c to A.Z. and VV-B113 to C.W. and A.Z.).Publication History
Received:
04 November 2008
Accepted after minor revision:
30 April 2008
Publication Date:
22 November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200902/lookinside/thumbnails/10-1160-th08-11-0720-1.jpg)
Summary
During their journey from the blood stream to sites of inflammation polymorphonuclear leukocytes (PMN) release a wide panoply of granule proteins. Shortly after the PMN efflux, the extravasation of monocytes sets in and recent research provides evidence that the release of PMN granule proteins and monocyte extravasation are causally interrelated. Granule proteins seeded on the endothelium by adherent PMN allow direct activation and subsequent adhesion of monocytes. In addition, PMN granule components enhance the endothelial expression of cell adhesion molecules, efficiently supporting the arrest of monocytes at inflamed vessels. Moreover, granule proteins contribute to the fine tuning of the local chemokine network. Proteolytic modification of chemokines as well as enhancement of local chemokine synthesis lead to increased monocyte extravasation. Finally, PMN granule proteins exert direct chemotactic effects, a mechanism which is of special importance in the early recruitment of inflammatory monocytes. Hence, granule proteins modify the monocyte extravasation cascade in a multifaceted manner ensuring the efficiency of these mechanisms.
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References
- 1 Rebuck JW, Crowley JH. A method of studying leukocytic functions in vivo. Ann NY Acad Sci 1955; 59: 757-805.
- 2 Ward PA. Chemotoxis of mononuclear cells. J Exp Med 1968; 128: 1201-1221.
- 3 Gallin JI, Fletcher MP, Seligmann BE. et al. Human neutrophil-specific granule deficiency: a model to assess the role of neutrophil-specific granules in the evolution of the inflammatory response. Blood 1982; 59: 1317-1329.
- 4 Gombart AF, Koeffler HP. Neutrophil specific granule deficiency and mutations in the gene encoding transcription factor C/EBP(epsilon). Curr Opin Hematol 2002; 09: 36-42.
- 5 Chertov O, Ueda H, Xu LL. et al. Identification of human neutrophil-derived cathepsin G and azurocidin/ CAP37 as chemoattractants for mononuclear cells and neutrophils. J Exp Med 1997; 186: 739-747.
- 6 Chertov O, Michiel DF, Xu L. et al. Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem 1996; 271: 2935-2940.
- 7 De Yang, Chen Q, Schmidt AP. et al. LL-37, the neutrophil granule-nd epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 2000; 192: 1069-1074.
- 8 Borregaard N, Cowland JB. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 1997; 89: 3503-3521.
- 9 Levy O. Antimicrobial proteins and peptides: antiinfective molecules of mammalian leukocytes. J Leukoc Biol 2004; 76: 909-925.
- 10 Fleischmann J, Selsted ME, Lehrer RI. Opsonic activity of MCP-1 and MCP-2, cationic peptides from rabbit alveolar macrophages. Diagn Microbiol Infect Dis 1985; 03: 233-242.
- 11 Heinzelmann M, Platz A, Flodgaard H. et al. Heparin binding protein (CAP37) is an opsonin for Staphylococcus aureus and increases phagocytosis in monocytes. Inflammation 1998; 22: 493-507.
- 12 Soehnlein O, Kai-Larsen Y, Frithiof R. et al. Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages. J Clin Invest 2008; 118: 3491-3502.
- 13 Soehnlein O, Kenne E, Rotzius P. et al. Neutrophil secretion products regulate anti-bacterial activity in monocytes and macrophages. Clin Exp Immunol 2008; 151: 139-145.
- 14 Oppenheim JJ, Yang D. Alarmins: chemotactic activators of immune responses. Curr Opin Immunol 2005; 17: 359-365.
- 15 Oppenheim JJ, Tewary P, de la Rosa G. et al. Alarmins initiate host defense. Adv Exp Med Biol 2007; 601: 185-194.
- 16 Soehnlein O, Lindbom L. Neutrophil-derived azurocidin alarms the immune system. J Leukoc Biol 2009; 85: 344-351.
- 17 Kim M, Carman CV, Springer TA. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 2003; 301: 1720-1725.
- 18 Zernecke A, Shagdarsuren E, Weber C. Chemokines in atherosclerosis: an update. Arterioscler Thromb Vasc Biol 2008; 28: 1897-1908.
- 19 Weber C. Chemokines take centre stage in vascular biology. Thromb Haemost 2007; 97: 685-687.
- 20 von Hundelshausen P, Petersen F, Brandt E. Platelet-derived chemokines in vascular biology. Thromb Haemost 2007; 97: 704-713.
- 21 Schober A, Zernecke A. Chemokines in vascular remodeling. Thromb Haemost 2007; 97: 730-737.
- 22 Colditz IG, Schneider MA, Pruenster M. et al. Chemokines at large: in-vivo mechanisms of their transport, presentation and clearance. Thromb Haemost 2007; 97: 688-693.
- 23 Tanaka Y, Adams DH, Hubscher S. et al. T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1 beta. Nature 1993; 361: 79-82.
- 24 Spillmann D, Witt D, Lindahl U. Defining the interleukin-8-binding domain of heparan sulfate. J Biol Chem 1998; 273: 15487-15493.
- 25 Roscic-Mrkic B, Fischer M, Leemann C. et al. RANTES (CCL5) uses the proteoglycan CD44 as an auxiliary receptor to mediate cellular activation signals and HIV-1 enhancement. Blood 2003; 102: 1169-1177.
- 26 Strauss-Ayali D, Conrad SM, Mosser DM. Monocyte subpopulations and their differentiation patterns during infection. J Leukoc Biol 2007; 82: 244-252.
- 27 Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood 1989; 74: 2527-2534.
- 28 Ziegler-Heitbrock HW. Definition of human blood monocytes. J Leukoc Biol 2000; 67: 603-606.
- 29 Grage-Griebenow E, Flad HD, Ernst M. et al. Human MO subsets as defined by expression of CD64 and CD16 differ in phagocytic activity and generation of oxygen intermediates. Immunobiology 2000; 202: 42-50.
- 30 Szabo G, Miller-Graziano CL, Wu JY. et al. Differential tumor necrosis factor production by human monocyte subsets. J Leukoc Biol 1990; 47: 206-216.
- 31 Grage-Griebenow E, Lorenzen D, Fetting R. et al. Phenotypical and functional characterization of Fc gamma receptor I (CD64)-negative monocytes, a minor human monocyte subpopulation with high accessory and antiviral activity. Eur J Immunol 1993; 23: 3126-3135.
- 32 Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol 2007; 81: 584-592.
- 33 Weber C, Belge KU, von Hundelshausen P. et al. Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol 2000; 67: 699-704.
- 34 Ancuta P, Rao R, Moses A. et al. Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. J Exp Med 2003; 197: 1701-1707.
- 35 Ancuta P, Moses A, Gabuzda D. Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions. Immunobiology 2004; 209: 11-20.
- 36 Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 2003; 19: 71-82.
- 37 Imhof BA, Aurrand-Lions M. Adhesion mechanisms regulating the migration of monocytes. Nat Rev Immunol 2004; 04: 432-444.
- 38 Boring L, Gosling J, Chensue SW. et al. Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J Clin Invest 1997; 100: 2552-2561.
- 39 Merad M, Manz MG, Karsunky H. et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol 2002; 03: 1135-1141.
- 40 Jung S, Aliberti J, Graemmel P. et al. Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 2000; 20: 4106-4114.
- 41 Landsman L, Bar-On L, Zernecke A. et al. CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 2009; 113: 963-972.
- 42 Merad M, Hoffmann P, Ranheim E. et al. Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versushost disease. Nat Med 2004; 10: 510-517.
- 43 Le Borgne M, Etchart N, Goubier A. et al. Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo. Immunity 2006; 24: 191-201.
- 44 Sunderkötter C, Nikolic T, Dillon MJ. et al. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol 2004; 172: 4410-4417.
- 45 Ginhoux F, Tacke F, Angeli V. et al. Langerhans cells arise from monocytes in vivo. Nat Immunol 2006; 07: 265-273.
- 46 Auffray C, Fogg D, Garfa M. et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 2007; 317: 666-670.
- 47 Soehnlein O, Zernecke A, Eriksson EE. et al. Neutrophil secretion products pave the way for inflammatory monocytes. Blood 2008; 112: 1461-1471.
- 48 Tapper H, Karlsson A, Mörgelin M. et al. Secretion of heparin-binding protein from human neutrophils is determined by its localization in azurophilic granules and secretory vesicles. Blood 2000; 99: 1785-1793.
- 49 Witko-Sarsat V, Cramer EM, Hieblot C. et al. Presence of proteinase 3 in secretory vesicles: evidence of a novel, highly mobilizable intracellular pool distinct from azurophil granules. Blood 1999; 94: 2487-2496.
- 50 Olofsson AM, Vestberg M, Herwald H. et al. Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis. J Clin Invest 1999; 104: 885-894.
- 51 Soehnlein O, Xie X, Ulbrich H. et al. Neutrophilderived heparin-binding protein (HBP/CAP37) deposited on endothelium enhances monocyte arrest under flow conditions. J Immunol 2005; 174: 6399-6405.
- 52 Brachemi S, Mambole A, Fakhouri F. et al. Increased membrane expression of proteinase 3 during neutrophil adhesion in the presence of anti proteinase 3 antibodies. J Am Soc Nephrol 2007; 18: 2330-2339.
- 53 Taekema-Roelvink ME, Van Kooten C, Heemskerk E. et al. Proteinase 3 interacts with a 111-kD membrane molecule of human umbilical vein endothelial cells. J Am Soc Nephrol 2000; 11: 640-648.
- 54 Lee TD, Gonzalez ML, Kumar P. et al. CAP37, a novel inflammatory mediator: its expression in endothelial cells and localization to atherosclerotic lesions. Am J Pathol 2002; 160: 841-848.
- 55 Pereira HA, Kumar P, Grammas P. Expression of CAP37, a novel inflammatory mediator, in Alzheimer’s disease. Neurobiol Aging 1996; 17: 753-759.
- 56 Påhlman LI, Mörgelin M, Eckert J. et al. Streptococcal M protein: a multipotent and powerful inducer of inflammation. J Immunol 2006; 177: 1221-1228.
- 57 Heinzelmann M, Mercer-Jones MA, Flodgaard H. et al. Heparin-binding protein (CAP37) is internalized in monocytes and increases LPS-induced monocyte activation. J Immunol 1998; 160: 5530-5536.
- 58 David A, Kacher Y, Specks U. et al. Interaction of proteinase 3 with CD11b/CD18 (beta2 integrin) on the cell membrane of human neutrophils. J Leukoc Biol 2003; 74: 551-557.
- 59 von Hundelshausen P, Weber KS, Huo Y. et al. RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation 2001; 103: 1772-1777.
- 60 Gautam N, Olofsson AM, Herwald H. et al. Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked alteration of vascular permeability. Nat Med 2001; 07: 1123-1127.
- 61 Soehnlein O, Oehmcke S, Ma X. et al. Neutrophil degranulation mediates severe lung damage triggered by streptococcal M1 protein. Eur Respir J 2008; 32: 405-412.
- 62 Herwald H, Cramer H, Mörgelin M. et al. M protein, a classical bacterial virulence determinant, forms complexes with fibrinogen that induce vascular leakage. Cell 2004; 116: 367-379.
- 63 Pereira HA, Moore P, Grammas P. CAP37, a neutrophil granule-derived protein stimulates protein kinase C activity in endothelial cells. J Leukoc Biol 1996; 60: 415-422.
- 64 Lee TD, Gonzalez ML, Kumar P. et al. CAP37, a neutrophil-derived inflammatory mediator, augments leukocyte adhesion to endothelial monolayers. Microvasc Res 2003; 66: 38-48.
- 65 Taekema-Roelvink ME, Kooten C, Kooij SV. et al. Proteinase 3 enhances endothelial monocyte chemoattractant protein-1 production and induces increased adhesion of neutrophils to endothelial cells by upregulating intercellular cell adhesion molecule-1. J Am Soc Nephrol 2001; 12: 932-940.
- 66 Chaly YV, Paleolog EM, Kolesnikova TS. et al. Neutrophil alpha-defensin human neutrophil peptide modulates cytokine production in human monocytes and adhesion molecule expression in endothelial cells. Eur Cytokine Netw 2000; 11: 257-266.
- 67 Edfeldt K, Agerberth B, Rottenberg ME. et al. Involvement of the antimicrobial peptide LL-37 in human atherosclerosis. Arterioscler Thromb Vasc Biol 2006; 26: 1551-1557.
- 68 Heinzelmann M, Kim E, Hofmeister A. et al. Heparin binding protein (CAP37) differentially modulates endotoxin-induced cytokine production. Int J Surg Investig 2001; 02: 457-466.
- 69 Heinzelmann M, Platz A, Flodgaard H. et al. Endocytosis of heparin-binding protein (CAP37) is essential for the enhancement of lipopolysaccharide-induced TNF-alpha production in human monocytes. J Immunol 1999; 162: 4240-4245.
- 70 Tjabringa GS, Aarbiou J, Ninaber DK. et al. The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. J Immunol 2003; 171: 6690-6696.
- 71 Bowdish DM, Davidson DJ, Speert DP. et al. The human cationic peptide LL-37 induces activation of the extracellular signal-regulated kinase and p38 kinase pathways in primary human monocytes. J Immunol 2004; 172: 3758-3765.
- 72 Van Wetering S, Mannesse-Lazeroms SP, Dijkman JH. et al. Effect of neutrophil serine proteinases and defensins on lung epithelial cells: modulation of cytotoxicity and IL-8 production. J Leukoc Biol 1997; 62: 217-226.
- 73 Van Wetering S, Mannesse-Lazeroms SP, Van Sterkenburg MA. et al. Effect of defensins on interleukin-8 synthesis in airway epithelial cells. Am J Physiol 1997; 272: L888-896.
- 74 Liu CY, Lin HC, Yu CT. et al. The concentration-dependent chemokine release and pro-apoptotic effects of neutrophil-derived alpha-defensin-1 on human bronchial and alveolar epithelial cells. Life Sci 2007; 80: 749-758.
- 75 Khine AA, Del Sorbo L, Vaschetto R. et al. Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway. Blood 2006; 107: 2936-2942.
- 76 Pham CT. Neutrophil serine proteases: specific regulators of inflammation. Nat Rev Immunol 2006; 06: 541-50.
- 77 Wiedow O, Meyer-Hoffert U. Neutrophil serine proteases: potential key regulators of cell signalling during inflammation. J Intern Med 2005; 257: 319-328.
- 78 Padrines M, Wolf M, Walz A. et al. Interleukin-8 processing by neutrophil elastase, cathepsin G and proteinase-3. FEBS Lett 1994; 352: 231-235.
- 79 Nufer O, Corbett M, Walz A. Amino-terminal processing of chemokine ENA-78 regulates biological activity. Biochemistry 1999; 38: 636-642.
- 80 Berahovich RD, Miao Z, Wang Y. et al. Proteolytic activation of alternative CCR1 ligands in inflammation. J Immunol 2005; 174: 7341-7351.
- 81 Wittamer V, Bondue B, Guillabert A. et al. Neutrophil-mediated maturation of chemerin: a link between innate and adaptive immunity. J Immunol 2005; 175: 487-493.
- 82 Rao RM, Betz TV, Lamont DJ. et al. Elastase release by transmigrating neutrophils deactivates endothelialbound SDF-1 α and attenuates subsequent T lymphocyte transendothelial migration. J Exp Med 2004; 200: 713-724.
- 83 Ryu OH, Choi SJ, Firatli E. et al. Proteolysis of macrophage inflammatory protein-1α isoforms LD78β and LD78α by neutrophil-derived serine proteases. J Biol Chem 2005; 280: 17415-17421.
- 84 Black RA, Rauch CT, Kozlosky CJ. et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells. Nature 1997; 385: 729-733.
- 85 Thornberry NA, Bull HG, Calaycay JR. et al. A novel heterodimeric cysteine protease is required for interleukin-1β processing in monocytes. Nature 1992; 356: 768-774.
- 86 Robache-Gallea S, Morand V, Bruneau JM. et al. In vitro processing of human tumor necrosis factor-α. J Biol Chem 1995; 270: 23688-23692.
- 87 Coeshott C, Ohnemus C, Pilyavskaya A. et al. Converting enzyme-independent release of tumor necrosis factor α and IL-1β from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3. Proc Natl Acad Sci USA 1999; 96: 6261-6266.
- 88 Territo MC, Ganz T, Selsted ME. et al. Monocytechemotactic activity of defensins from human neutrophils. J Clin Invest 1989; 84: 2017-2020.
- 89 Arnold L, Henry A, Poron F. et al. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med 2007; 204: 1057-1069.
- 90 Nahrendorf M, Swirski FK, Aikawa E. et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 2007; 204: 3037-3047.
- 91 Robben PM, LaRegina M, Kuziel WA. et al. Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis. J Exp Med 2005; 201: 1761-1769.
- 92 Tacke F, Alvarez D, Kaplan TJ. et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 2007; 117: 185-194.
- 93 Scapini P, Lapinet-Vera JA, Gasperini S. et al. The neutrophil as a cellular source of chemokines. Immunol Rev 2000; 177: 195-203.
- 94 Weber C, Koenen RR. Fine-tuning leukocyte responses: towards a chemokine ‘interactome’. Trends Immunol 2006; 27: 268-273.
- 95 Lekstrom-Himes JA, Gallin JI. Immunodeficiency diseases caused by defects in phagocytes. N Engl J Med 2000; 343: 1703-1714.
- 96 Dale DC, Boxer L, Liles WC. The phagocytes: neutrophils and monocytes. Blood 2008; 112: 935-945.
- 97 Pham CT, Ivanovich JL, Raptis SZ. et al. Papillon-efèvre syndrome: correlating the molecular, cellular, and clinical consequences of cathepsin C/dipeptidyl peptidase I deficiency in humans. J Immunol 2004; 173: 7277-7281.
- 98 Weber C, Zernecke A, Libby P. The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models. Nat Rev Immunol 2008; 08: 802-815.
- 99 Zernecke A, Bot I, Djalali-Talab Y. et al. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis. Circ Res 2008; 102: 209-217.