Galectin-3 aggravates experimental polymicrobial sepsis by impairing neutrophil recruitment to the infectious focus

被引:19
作者
Ferreira, Raphael G. [1 ]
Rodrigues, Lilian C. [2 ]
Nascimento, Daniele C. [1 ]
Kanashiro, Alexandre [1 ]
Melo, Paulo H. [1 ]
Borges, Vanessa F. [1 ]
Gozzi, Aline [3 ]
Prado, Douglas da Silva [1 ]
Borges, Marcos C. [3 ]
Ramalho, Fernando S. [4 ]
Stowell, Sean R. [5 ]
Cummings, Richard D. [6 ]
Dias-Baruffi, Marcelo [2 ]
Cunha, Fernando Q. [1 ]
Alves-Filho, Jose C. [1 ]
机构
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP, Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto, SP, Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto, SP, Brazil
[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol, Ribeirao Preto, SP, Brazil
[5] Emory Univ, Dept Pathol, Sch Med, Atlanta, GA 30322 USA
[6] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA
基金
巴西圣保罗研究基金会;
关键词
Sepsis; CLP; Galectin-3; Neutrophil; INTERNATIONAL CONSENSUS DEFINITIONS; AIRWAY EPITHELIAL-CELLS; SEPTIC SHOCK; MOLECULAR-PATTERNS; BINDS; LECTINS;
D O I
10.1016/j.jinf.2018.06.010
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Sepsis is an overwhelming systemic inflammation resulting from an uncontrolled infection that causes extensive tissue damage, organ dysfunction and eventually death. A growing body of evidence indicates that impaired neutrophil migration to the site of infection is associated with poor outcome in sepsis. Here we show that galectin-3 (Gal-3), an endogenous glycan-binding protein, plays a critical role in sepsis outcome. We found that serum Gal-3 concentration increased in patients with septic shock and mice undergoing sepsis induced by cecal ligation and puncture (CLP). Mice deficient in Gal-3 (Gal-3 KO) are more resistant to sepsis induced by CLP, showing lower levels of biochemical markers and neutrophil infiltration for organ injury/dysfunction than those observed in wild-type mice (WT). Furthermore, Gal-3 KO mice show an increased number of neutrophils in the primary focus of infection and reduced bacterial loads in the peritoneal cavity, blood, and lungs. Mechanistically, blood neutrophils from septic mice show higher levels of surface-bound Gal-3 than neutrophils from naive mice. The deficiency of Gal-3 was associated with increased rolling and adhesion of these cells in mesenteric venules. Our results indicate that Gal-3, secreted during sepsis, inhibits neutrophil migration into the infectious focus, which promotes the bacterial spread and worsens the outcome of sepsis. (C) 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:391 / 397
页数:7
相关论文
共 43 条
[1]   New Definitions for Sepsis and Septic Shock Continuing Evolution but With Much Still to Be Done [J].
Abraham, Edward .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2016, 315 (08) :757-759
[2]   Toll-like receptor 4 signaling leads to neutrophil migration impairment in polymicrobial sepsis [J].
Alves, JC ;
de Freitas, A ;
Russo, M ;
Cunha, FQ .
CRITICAL CARE MEDICINE, 2006, 34 (02) :461-470
[3]   NEUTROPHIL PARALYSIS IN SEPSIS [J].
Alves-Filho, Jose C. ;
Spiller, Fernando ;
Cunha, Fernando Q. .
SHOCK, 2010, 34 :15-21
[4]   Galectin-3 inhibits the chemotaxis of human polymorphonuclear neutrophils in vitro [J].
Baseras, Billur ;
Gaida, Matthias M. ;
Kahle, Nadine ;
Schuppel, Ann-Kathrin ;
Kathrey, Diana ;
Prior, Birgit ;
Wente, Moritz ;
Haensch, Gertrud Maria .
IMMUNOBIOLOGY, 2012, 217 (01) :83-90
[5]   Microbe-host interacions are positively and negatively regulated by galectin glycan interactions [J].
Baum, Linda G. ;
Garner, Omai B. ;
Schaefer, Katrin ;
Lee, Benhur .
FRONTIERS IN IMMUNOLOGY, 2014, 5
[6]   The immunopathogenesis of sepsis [J].
Cohen, J .
NATURE, 2002, 420 (6917) :885-891
[7]   Sepsis: a roadmap for future research [J].
Cohen, Jonathan ;
Vincent, Jean-Louis ;
Adhikari, Neill K. J. ;
Machado, Flavia R. ;
Angus, Derek C. ;
Calandra, Thierry ;
Jaton, Katia ;
Giulieri, Stefano ;
Delaloye, Julie ;
Opal, Steven ;
Tracey, Kevin ;
van der Poll, Tom ;
Pelfrene, Eric .
LANCET INFECTIOUS DISEASES, 2015, 15 (05) :581-614
[8]   Cecal ligation and puncture: the gold standard model for polymicrobial sepsis? [J].
Dejager, Lien ;
Pinheiro, Iris ;
Dejonckheere, Eline ;
Libert, Claude .
TRENDS IN MICROBIOLOGY, 2011, 19 (04) :198-208
[9]   Damage- and Pathogen-Associated Molecular Patterns and Alarmins: Keys to Sepsis? [J].
Denk, S. ;
Perl, M. ;
Huber-Lang, M. .
EUROPEAN SURGICAL RESEARCH, 2012, 48 (04) :171-179
[10]   Sepsis: Current Dogma and New Perspectives [J].
Deutschman, Clifford S. ;
Tracey, Kevin J. .
IMMUNITY, 2014, 40 (04) :464-476