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ISSN: 1734-1922
Archives of Medical Science
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3/2018
vol. 14
 
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abstract:
Experimental research

Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice

Qing Cao, Biru Li, Xike Wang, Kun Sun, Ying Guo

Arch Med Sci 2018; 14, 3: 635–644
Online publish date: 2017/01/06
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Introduction
Sustained neutrophilic infiltration is known to contribute to organ damage, such as acute lung injury (ALI). CXC chemokine receptor 2 (CXCR2) is the major receptor regulating inflammatory neutrophil recruitment in acute and chronic inflamed tissues. The purpose of this study was to investigate the functional relevance of the CXCR2 inhibitor SB225002 in LPS-induced acute lung injury.

Material and methods
Male C57BL/6 mice were randomly divided into the following four experimental groups (n = 10 per group): untreated group (control group, Ctr); LPS-treated ALI group (LPS group, LPS); LPS + PBS-treated group (LPS + PBS); and SB225002-treated ALI group (LPS + SB225002). Twenty-four hours after treatment, the blood, bronchoalveolar lavage fluid (BALF), and lung tissue were collected and wet/dry ratio, protein concentration, myeloperoxidase (MPO) activity, neutrophil infiltration, and inflammatory cytokine secretion in lung tissue were measured. The pathologic changes in the lungs were examined using optical microscopy. Survival rates were recorded at 120 h in all four groups, in other experiments.

Results
Histology findings revealed that the SB225002-treated group had significantly milder lung injury compared to the LPS-induced ALI and the PBS-treated control groups. Treatment with SB225002 significantly attenuated LPS-induced lung injury and suppressed the inflammatory responses in damaged lung tissue. Compared to the PBS-treated control group, treatment with SB225002 dramatically decreased the lung wet/dry ratio, protein concentration, and infiltration of neutrophils in lung tissue. Therefore, SB225002 treatment appeared to inhibit the production of inflammatory cytokines and increase survival time compared to the PBS-treated control group.

Conclusions
Together, these data demonstrated that inhibition of CXCR2 signaling by SB225002 could ameliorate LPS-induced acute lung injury, by reducing neutrophil recruitment and vascular permeability. SB225002 may be further developed as a potential novel treatment for LPS-induced ALI.

keywords:

SB225002, LPS-induced ALI, CXCR2, neutrophil migration

references:
Matthay MA, Ware LB, Zimmerman GA. The acute respiratory distress syndrome. J Clin Invest 2012; 122: 2731-40.
Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000; 342: 1334-49.
Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med 2005; 353: 1685-93.
Erickson SE, Martin GS, Davis JL, Matthay MA, Eisner MD. Recent trends in acute lung injury mortality: 1996-2005. Crit Care Med 2009; 37: 1574-9.
Matthay MA, Zimmerman GA, Esmon C, et al. Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group. Am J Respir Crit Care Med 2003; 167: 1027-35.
Martin TR. Neutrophils and lung injury: getting it right. J Clin Invest 2002; 110: 1603-5.
Baggiolini M. Chemokines in pathology and medicine. J Intern Med 2001; 250: 91-104.
Dumont RA, Car BD, Voitenok NN, et al. Systemic neutralization of interleukin-8 markedly reduces neutrophilic pleocytosis during experimental lipopolysaccharide-induced meningitis in rabbits. Infect Immun 2000; 68:5756-63.
Murphy PM. Neutrophil receptors for interleukin-8 and related CXC chemokines. Semin Hematol 1997; 34: 311-8.
Stillie R, Farooq SM, Gordon JR, Stadnyk AW. The functional significance behind expressing two IL-8 receptor types on PMN. J Leukoc Biol 2009; 86: 529-43.
Christopher MJ, Link DC. Regulation of neutrophil homeostasis. Curr Opin Hematol 2007; 14: 3-8.
von Vietinghoff S, Ley K. Homeostatic regulation of blood neutrophil counts. J Immunol 2008; 181: 5183-8.
Doerschuk CM. Mechanisms of leukocyte sequestration in inflamed lungs. Microcirculation 2001; 8: 71-88.
Belperio JA, Keane MP, Burdick MD, et al. Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator-induced lung injury. J Clin Invest 2002; 110: 1703-16.
Reutershan J, Morris MA, Burcin TL, et al. Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung. J Clin Invest 2006; 116: 695-702.
Keane MP, Belperio JA, Moore TA, et al. Neutralization of the CXC chemokine, macrophage inflammatory protein-2, attenuates bleomycin-induced pulmonary fibrosis. J Immunol 1999; 162: 5511-8.
Colletti LM, Kunkel SL, Walz A, et al. Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein. J Clin Invest 1995; 95: 134-41.
Gray KD, Simovic MO, Chapman WC, et al. Endotoxin potentiates lung injury in cerulein-induced pancreatitis. Am J Surg 2003; 186: 526-30.
Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Invest 2006; 116: 3211-9.
Suratt BT, Young SK, Lieber J, Nick JA, Henson PM, Worthen GS. Neutrophil maturation and activation determine anatomic site of clearance from circulation. Am J Physiol Lung Cell Mol Physiol 2001; 281: L913-21.
Haslett C, Worthen GS, Giclas PC, Morrison DC, Henson JE, Henson PM. The pulmonary vascular sequestration of neutrophils in endotoxemia is initiated by an effect of endotoxin on the neutrophil in the rabbit. Am Rev Respir Dis 1987; 136: 9-18.
Farooq SM, Stillie R, Svensson M, Svanborg C, Strieter RM, Stadnyk AW. Therapeutic effect of blocking CXCR2 on neutrophil recruitment and dextran sodium sulfate-induced colitis. J Pharmacol Exp Ther 2009; 329: 123-9.
Grommes J, Soehnlein O. Contribution of neutrophils to acute lung injury. Mol Med 2011; 17: 293-307.
Ahuja SK, Lee JC, Murphy PM. CXC chemokines bind to unique sets of selectivity determinants that can function independently and are broadly distributed on multiple domains of human interleukin-8 receptor B. Determinants of high affinity binding and receptor activation are distinct. J Biol Chem 1996; 271: 225-32.
Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI. Structure and functional expression of a human interleukin-8 receptor. Science 1991; 253: 1278-80.
Murphy PM, Tiffany HL. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science 1991; 253: 1280-3.
Reutershan J, Basit A, Galkina EV, Ley K. Sequential recruitment of neutrophils into lung and bronchoalveolar lavage fluid in LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol 2005; 289: L807-15.
Liu L, Li M, Spangler LC, et al. Functional defect of peripheral neutrophils in mice with induced deletion of CXCR2. Genesis 2013; 51: 587-95.
Eash KJ, Greenbaum AM, Gopalan PK, Link DC. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest 2010; 120: 2423-31.
Wu Y, Wang S, Farooq SM, et al. A chemokine receptor CXCR2 macromolecular complex regulates neutrophil functions in inflammatory diseases. J Biol Chem 2012; 287: 5744-55.
Abraham E. Neutrophils and acute lung injury. Crit Care Med 2003; 31 (4 Suppl.): S195-9.
Azoulay E, Lemiale V, Mokart D, et al. Acute respiratory distress syndrome in patients with malignancies. Intensive Care Med 2014; 40: 1106-14.
de Luis Cabezon N, Sanchez Castro I, Bengoetxea Uriarte UX, Rodrigo Casanova MP, Garcia Pena JM, Aguilera Celorrio L. Acute respiratory distress syndrome: A review of the Berlin definition [Spanish]. Rev Esp Anestesiol Reanim 2014; 61: 319-27.
Walter JM, Wilson J, Ware LB. Biomarkers in acute respiratory distress syndrome: from pathobiology to improving patient care. Expert Rev Respir Med 2014; 8: 573-86.
Buanne P, Di Carlo E, Caputi L, et al. Crucial pathophysiological role of CXCR2 in experimental ulcerative colitis in mice. J Leukoc Biol 2007; 82: 1239-46.
White JR, Lee JM, Young PR, et al. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem 1998; 273: 10095-8.
Sue RD, Belperio JA, Burdick MD, et al. CXCR2 is critical to hyperoxia-induced lung injury. J Immunol 2004; 172: 3860-8.
Strieter RM, Keane MP, Burdick MD, Sakkour A, Murray LA, Belperio JA. The role of CXCR2/CXCR2 ligands in acute lung injury. Curr Drug Targets Inflamm Allergy 2005; 4: 299-303.
Zarbock A, Allegretti M, Ley K. Therapeutic inhibition of CXCR2 by reparixin attenuates acute lung injury in mice. Br J Pharmacol 2008; 155: 357-64.
Lomas-Neira JL, Chung CS, Grutkoski PS, Miller EJ, Ayala A. CXCR2 inhibition suppresses hemorrhage-induced priming for acute lung injury in mice. J Leukoc Biol 2004; 76: 58-64.
Donnelly LE, Barnes PJ. Chemokine receptor CXCR2 antagonism to prevent airway inflammation. Drugs Future 2011; 36: 465-72.
Holz O, Khalilieh S, Ludwig-Sengpiel A, et al. SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects. Eur Respir J 2010; 35: 564-70.
Lazaar AL, Sweeney LE, MacDonald AJ, Alexis NE, Chen C, Tal-Singer R. SB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans. Br J Clin Pharmacol 2011; 72: 282-93.
Leaker BR, Barnes PJ, O’Connor B. Inhibition of LPS-induced airway neutrophilic inflammation in healthy volunteers with an oral CXCR2 antagonist. Respir Res 2013; 14: 137.
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