Heparin-binding protein (HBP/CAP37) - a link to endothelin-1 in endotoxemia-induced pulmonary oedema?

Acta Anaesthesiologica ScandinavicaVolume 58, Issue 5 p. 549-559 Intensive Care and Physiology Heparin-binding protein (HBP/CAP37) – a link to endothelin-1 in endotoxemia-induced pulmonary oedema? B. P. PERSSON, Corresponding Author B. P. PERSSON Department of Anaesthesiology, Surgical Services and Intensive Care, Karolinska University Hospital, Solna, Sweden Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden Address: Björn P. Persson Department of Anaesthesiology, Surgical Services and Intensive Care Karolinska University Hospital SE-171 76 Solna, Stockholm Sweden e-mail: [email protected]Search for more papers by this authorH. HALLDORSDOTTIR, H. HALLDORSDOTTIR Department of Anaesthesiology, Surgical Services and Intensive Care, Karolinska University Hospital, Solna, Sweden Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorL. LINDBOM, L. LINDBOM Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorP. ROSSI, P. ROSSI Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, SwedenSearch for more papers by this authorH. HERWALD, H. HERWALD Department of Clinical Sciences, University of Lund, Lund, SwedenSearch for more papers by this authorE. WEITZBERG, E. WEITZBERG Department of Anaesthesiology, Surgical Services and Intensive Care, Karolinska University Hospital, Solna, Sweden Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorA. OLDNER, A. OLDNER Department of Anaesthesiology, Surgical Services and Intensive Care, Karolinska University Hospital, Solna, Sweden Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this author B. P. PERSSON, Corresponding Author B. P. PERSSON Department of Anaesthesiology, Surgical Services and Intensive Care, Karolinska University Hospital, Solna, Sweden Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden Address: Björn P. Persson Department of Anaesthesiology, Surgical Services and Intensive Care Karolinska University Hospital SE-171 76 Solna, Stockholm Sweden e-mail: [email protected]Search for more papers by this authorH. HALLDORSDOTTIR, H. HALLDORSDOTTIR Department of Anaesthesiology, Surgical Services and Intensive Care, Karolinska University Hospital, Solna, Sweden Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorL. LINDBOM, L. LINDBOM Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorP. ROSSI, P. ROSSI Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, SwedenSearch for more papers by this authorH. HERWALD, H. HERWALD Department of Clinical Sciences, University of Lund, Lund, SwedenSearch for more papers by this authorE. WEITZBERG, E. WEITZBERG Department of Anaesthesiology, Surgical Services and Intensive Care, Karolinska University Hospital, Solna, Sweden Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorA. OLDNER, A. OLDNER Department of Anaesthesiology, Surgical Services and Intensive Care, Karolinska University Hospital, Solna, Sweden Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this author First published: 11 March 2014 https://doi.org/10.1111/aas.12301Citations: 12Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Background Vascular leakage and oedema formation are key components in sepsis. In septic patients, plasma levels of the vasoconstrictive and pro-inflammatory peptide endothelin-1 (ET-1) correlate with mortality. During sepsis, neutrophils release heparin-binding protein (HBP) known to increase vascular permeability and to be a promising biomarker of human sepsis. As disruption of ET-signalling in endotoxemia attenuates formation of oedema, we hypothesized that this effect could be related to decreased levels of HBP. To investigate this, we studied the effects of ET-receptor antagonism on plasma HBP and oedema formation in a porcine model of sepsis. In addition, to further characterize a potential endothelin/HBP interaction, we investigated the effects of graded ET-receptor agonist infusions. Methods Sixteen anesthetized pigs were subjected to 5 h of endotoxemia and were randomized to receive either the ET-receptor antagonist tezosentan or vehicle after 2 h. Haemodynamics, gas-exchange and lung water were monitored. In separate experiments, plasma HBP was measured in eight non-endotoxemic animals exposed to graded infusion of ET-1 or sarafotoxin 6c. Results Endotoxemia increased plasma ET-1, plasma HBP, and extravascular lung water. Tezosentan-treatment markedly attenuated plasma HBP and extravascular lung water, and these parameters correlated significantly. Tezosentan decreased pulmonary vascular resistance and increased respiratory compliance. In non-endotoxemic pigs graded ET-1 and sarafotoxin 6c infusions caused a dose-dependent increase in plasma HBP. Conclusions ET-receptor antagonism reduces porcine endotoxin-induced pulmonary oedema and plasma levels of the oedema-promoting protein HBP. Moreover, direct ET-receptor stimulation distinctively increases plasma HBP. Together, these results suggest a novel mechanism by which ET-1 contributes to formation of oedema during experimental sepsis. References 1 Lee WL, Slutsky AS. Sepsis and endothelial permeability. N Engl J Med 2010; 363: 689–691. 10.1056/NEJMcibr1007320 CASPubMedWeb of Science®Google Scholar 2 Annane D, Bellissant E, Cavaillon J. Septic shock. Lancet 2005; 365: 63–78. 10.1016/S0140-6736(04)17667-8 CASPubMedWeb of Science®Google Scholar 3 Wanecek M, Weitzberg E, Rudehill A, Oldner A. The endothelin system in septic and endotoxin shock. Eur J Pharmacol 2000; 407: 1–15. 10.1016/S0014-2999(00)00675-0 CASPubMedWeb of Science®Google Scholar 4 Barton M, Yanagisawa M. Endothelin: 20 years from discovery to therapy. Can J Physiol Pharmacol 2008; 86: 485–498. 10.1139/Y08-059 CASPubMedWeb of Science®Google Scholar 5 de Nucci G, Thomas R, D'Orleans-Juste P, Antunes E, Walder C, Warner TD, Vane JR. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci U S A 1988; 85: 9797–9800. 10.1073/pnas.85.24.9797 CASPubMedWeb of Science®Google Scholar 6 Fukuroda T, Fujikawa T, Ozaki S, Ishikawa K, Yano M, Nishikibe M. Clearance of circulating endothelin-1 by ETB receptors in rats. Biochem Biophys Res Commun 1994; 199: 1461–1465. 10.1006/bbrc.1994.1395 CASPubMedWeb of Science®Google Scholar 7 Persson BP, Rossi P, Weitzberg E, Oldner A. Inhaled tezosentan reduces pulmonary hypertension in endotoxin-induced lung injury. Shock 2009; 32: 427–434. 10.1097/SHK.0b013e31819e2cbb CASWeb of Science®Google Scholar 8 Rossi P, Wanecek M, Konrad D, Oldner A. Tezosentan counteracts endotoxin-induced pulmonary edema and improves gas exchange. Shock 2004; 21: 543–548. 10.1097/01.shk.0000126147.76311.18 CASPubMedWeb of Science®Google Scholar 9 Kuklin VN, Kirov MY, Evgenov OV, Sovershaev MA, Sjoberg J, Kirova SS, Bjertnaes LJ. Novel endothelin receptor antagonist attenuates endotoxin-induced lung injury in sheep. Crit Care Med 2004; 32: 766–773. 10.1097/01.CCM.0000114575.08269.F6 CASPubMedWeb of Science®Google Scholar 10 Comellas AP, Briva A. Role of endothelin-1 in acute lung injury. Transl Res 2009; 153: 263–271. 10.1016/j.trsl.2009.02.007 CASPubMedWeb of Science®Google Scholar 11 Gautam N, Olofsson AM, Herwald H, Iversen LF, Lundgren-Akerlund E, Hedqvist P, Arfors KE, Flodgaard H, Lindbom L. Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked alteration of vascular permeability. Nat Med 2001; 7: 1123–1127. 10.1038/nm1001-1123 CASPubMedWeb of Science®Google Scholar 12 Rasmussen PB, Bjorn S, Hastrup S, Nielsen PF, Norris K, Thim L, Wiberg FC, Flodgaard H. Characterization of recombinant human HBP/CAP37/azurocidin, a pleiotropic mediator of inflammation-enhancing LPS-induced cytokine release from monocytes. FEBS Lett 1996; 390: 109–112. 10.1016/0014-5793(96)00639-4 CASPubMedWeb of Science®Google Scholar 13 Soehnlein O, Lindbom L. Neutrophil-derived azurocidin alarms the immune system. J Leukoc Biol 2009; 85: 344–351. 10.1189/jlb.0808495 CASPubMedWeb of Science®Google Scholar 14 Linder A, Christensson B, Herwald H, Bjorck L, Akesson P. Heparin-binding protein: an early marker of circulatory failure in sepsis. Clin Infect Dis 2009; 49: 1044–1050. 10.1086/605563 CASPubMedWeb of Science®Google Scholar 15 Linder A, Akesson P, Inghammar M, Treutiger CJ, Linner A, Sunden-Cullberg J. Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock. Crit Care 2012; 16: R90. 10.1186/cc11353 PubMedWeb of Science®Google Scholar 16 Zarpelon AC, Pinto LG, Cunha TM, Vieira SM, Carregaro V, Souza GR, Silva JS, Ferreira SH, Cunha FQ, Verri WA Jr. Endothelin-1 induces neutrophil recruitment in adaptive inflammation via TNF-alpha and CXCL1/CXCR2 in mice. Can J Physiol Pharmacol 2012; 90: 187–199. 10.1139/y11-116 CASPubMedWeb of Science®Google Scholar 17 Eibl G, Hotz HG, Faulhaber J, Kirchengast M, Buhr HJ, Foitzik T. Effect of endothelin and endothelin receptor blockade on capillary permeability in experimental pancreatitis. Gut 2000; 46: 390–394. 10.1136/gut.46.3.390 CASPubMedWeb of Science®Google Scholar 18 Persson BP, Rossi P, Weitzberg E, Lindbom L, Oldner A. The ET-receptor antagonist tezosentan attenuate pulmonary edema and reduces levels of the neutrophil-derived permeability-promoting protein HBP in experimental sepsis: a novel potential link between ET-1 and edema formation? Intensive Care Med 2011; 37 (Suppl. 1): S219. Google Scholar 19 Pearce ML, Yamashita J, Beazell J. Measurement of pulmonary edema. Circ Res 1965; 16: 482–488. 10.1161/01.RES.16.5.482 CASPubMedWeb of Science®Google Scholar 20 Selinger SL, Bland RD, Demling RH, Staub NC. Distribution volumes of [131I] albumin, [14C] sucrose, and 36Cl in sheep lung. J Appl Physiol 1975; 39: 773–779. 10.1152/jappl.1975.39.5.773 CASPubMedWeb of Science®Google Scholar 21 Sakka SG, Ruhl CC, Pfeiffer UJ, Beale R, McLuckie A, Reinhart K, Meier-Hellmann A. Assessment of cardiac preload and extravascular lung water by single transpulmonary thermodilution. Intensive Care Med 2000; 26: 180–187. 10.1007/s001340050043 CASPubMedWeb of Science®Google Scholar 22 Rossi P, Wanecek M, Rudehill A, Konrad D, Weitzberg E, Oldner A. Comparison of a single indicator and gravimetric technique for estimation of extravascular lung water in endotoxemic pigs. Crit Care Med 2006; 34: 1437–1443. 10.1097/01.CCM.0000215830.48977.29 PubMedWeb of Science®Google Scholar 23 Kirov MY, Kuzkov VV, Kuklin VN, Waerhaug K, Bjertnaes LJ. Extravascular lung water assessed by transpulmonary single thermodilution and postmortem gravimetry in sheep. Crit Care 2004; 8: R451–458. 10.1186/cc2974 PubMedWeb of Science®Google Scholar 24 Hemsen A. Biochemical and functional characterization of endothelin peptides with special reference to vascular effects. Acta Physiol Scand Suppl 1991; 602: 1–61. CASPubMedGoogle Scholar 25 Dingemanse J, Clozel M, van Giersbergen PL. Pharmacokinetics and pharmacodynamics of tezosentan, an intravenous dual endothelin receptor antagonist, following chronic infusion in healthy subjects. Br J Clin Pharmacol 2002; 53: 355–362. 10.1046/j.1365-2125.2002.01158.x CASPubMedWeb of Science®Google Scholar 26 Rossi P, Oldner A, Wanecek M, Leksell LG, Rudehill A, Konrad D, Weitzberg E. Comparison of gravimetric and a double-indicator dilution technique for assessment of extra-vascular lung water in endotoxaemia. Intensive Care Med 2003; 29: 460–466. 10.1007/s00134-002-1604-z CASPubMedWeb of Science®Google Scholar 27 Helset E, Kjaeve J, Hauge A. Endothelin-1-induced increases in microvascular permeability in isolated, perfused rat lungs requires leukocytes and plasma. Circ Shock 1993; 39: 15–20. CASPubMedWeb of Science®Google Scholar 28 Mencarelli M, Pecorelli A, Carbotti P, Valacchi G, Grasso G, Muscettola M. Endothelin receptor a expression in human inflammatory cells. Regul Pept 2009; 158: 1–5. 10.1016/j.regpep.2009.06.004 CASPubMedWeb of Science®Google Scholar 29 Wanecek M, Oldner A, Sundin P, Alving K, Weitzberg E, Rudehill A. Effects on haemodynamics by selective endothelin ET(B) receptor and combined endothelin ET(A)/ET(B) receptor antagonism during endotoxin shock. Eur J Pharmacol 1999; 386: 235–245. 10.1016/S0014-2999(99)00774-8 CASPubMedWeb of Science®Google Scholar 30 Urbanowicz W, Sogni P, Moreau R, Tazi KA, Barriere E, Poirel O, Lebrec D, Martin A, Guimont MC, Cazals-Hatem D. Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats. Gut 2004; 53: 1844–1849. 10.1136/gut.2003.036517 CASPubMedWeb of Science®Google Scholar Citing Literature Volume58, Issue5May 2014Pages 549-559 ReferencesRelatedInformation