The Role of Neutrophils in the Development of Liver Diseases

Overview

Journal Cell Mol Immunol

Date 2014 Mar 18

PMID 24633014

Citations 113

Authors

Ruonan Xu

Huihuang Huang

Zheng Zhang

Fu-Sheng Wang

Affiliations

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Abstract

Liver disease encompasses a wide variety of liver conditions, including liver failure, liver cirrhosis and a spectrum of acute and chronic hepatitis, such as alcoholic, fatty, drug, viral and chronic hepatitis. Liver injury is a primary causative factor in liver disease; generally, these factors include direct liver damage and immune-mediated liver injury. Neutrophils (also known as neutrophilic granulocytes or polymorphonuclear leukocytes (PMNs)) are the most abundant circulating white blood cell type in humans, and PMNs are a major innate immune cell subset. Inappropriate activation and homing of neutrophils to the microvasculature contributes to the pathological manifestations of many types of liver disease. This review summarizes novel concepts of neutrophil-mediated liver injury that are based on current clinical and animal model studies.

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References

Antoniades C, Berry P, Wendon J, Vergani D . The importance of immune dysfunction in determining outcome in acute liver failure. J Hepatol. 2008; 49(5):845-61. DOI: 10.1016/j.jhep.2008.08.009. View

Tsuda Y, Takahashi H, Kobayashi M, Hanafusa T, Herndon D, Suzuki F . Three different neutrophil subsets exhibited in mice with different susceptibilities to infection by methicillin-resistant Staphylococcus aureus. Immunity. 2004; 21(2):215-26. DOI: 10.1016/j.immuni.2004.07.006. View

Woodfin A, Voisin M, Nourshargh S . Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol. 2009; 17(1):9-17. PMC: 2882030. DOI: 10.1097/MOH.0b013e3283333930. View

Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro M . Macrophage polarization in tumour progression. Semin Cancer Biol. 2008; 18(5):349-55. DOI: 10.1016/j.semcancer.2008.03.004. View

Williams C, Farhood A, Jaeschke H . Role of caspase-1 and interleukin-1beta in acetaminophen-induced hepatic inflammation and liver injury. Toxicol Appl Pharmacol. 2010; 247(3):169-78. PMC: 2929281. DOI: 10.1016/j.taap.2010.07.004. View

Zhou S, Dai Z, Zhou Z, Wang X, Yang G, Wang Z . Overexpression of CXCL5 mediates neutrophil infiltration and indicates poor prognosis for hepatocellular carcinoma. Hepatology. 2012; 56(6):2242-54. DOI: 10.1002/hep.25907. View

Uchida Y, Freitas M, Zhao D, Busuttil R, Kupiec-Weglinski J . The protective function of neutrophil elastase inhibitor in liver ischemia/reperfusion injury. Transplantation. 2010; 89(9):1050-6. PMC: 3627371. DOI: 10.1097/TP.0b013e3181d45a98. View

Lawson J, Farhood A, HOPPER R, Bajt M, Jaeschke H . The hepatic inflammatory response after acetaminophen overdose: role of neutrophils. Toxicol Sci. 2000; 54(2):509-16. DOI: 10.1093/toxsci/54.2.509. View

Nathan C . Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006; 6(3):173-82. DOI: 10.1038/nri1785. View

10.

Gao B, Bataller R . Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011; 141(5):1572-85. PMC: 3214974. DOI: 10.1053/j.gastro.2011.09.002. View

11.

Wislez M, Rabbe N, Marchal J, Milleron B, Crestani B, Mayaud C . Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor progression and death. Cancer Res. 2003; 63(6):1405-12. View

12.

Kono H, Uesugi T, Froh M, Rusyn I, Bradford B, Thurman R . ICAM-1 is involved in the mechanism of alcohol-induced liver injury: studies with knockout mice. Am J Physiol Gastrointest Liver Physiol. 2001; 280(6):G1289-95. DOI: 10.1152/ajpgi.2001.280.6.G1289. View

13.

Taieb J, Delarche C, Ethuin F, Selloum S, Poynard T, Gougerot-Pocidalo M . Ethanol-induced inhibition of cytokine release and protein degranulation in human neutrophils. J Leukoc Biol. 2002; 72(6):1142-7. View

14.

Koo S . Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis. Clin Mol Hepatol. 2013; 19(3):210-5. PMC: 3796672. DOI: 10.3350/cmh.2013.19.3.210. View

15.

Ziol M, Tepper M, Lohez M, Arcangeli G, Ganne N, Christidis C . Clinical and biological relevance of hepatocyte apoptosis in alcoholic hepatitis. J Hepatol. 2001; 34(2):254-60. DOI: 10.1016/s0168-8278(00)00047-7. View

16.

Biyik M, Ucar R, Solak Y, Gungor G, Polat I, Gaipov A . Blood neutrophil-to-lymphocyte ratio independently predicts survival in patients with liver cirrhosis. Eur J Gastroenterol Hepatol. 2012; 25(4):435-41. DOI: 10.1097/MEG.0b013e32835c2af3. View

17.

Jaeschke H, Williams C, Ramachandran A, Bajt M . Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int. 2011; 32(1):8-20. PMC: 3586825. DOI: 10.1111/j.1478-3231.2011.02501.x. View

18.

Mookerjee R, Stadlbauer V, Lidder S, Wright G, Hodges S, Davies N . Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome. Hepatology. 2007; 46(3):831-40. DOI: 10.1002/hep.21737. View

19.

McDonald B, McAvoy E, Lam F, Gill V, de la Motte C, Savani R . Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. J Exp Med. 2008; 205(4):915-27. PMC: 2292228. DOI: 10.1084/jem.20071765. View

20.

Gao B, Seki E, Brenner D, Friedman S, Cohen J, Nagy L . Innate immunity in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol. 2011; 300(4):G516-25. PMC: 3774265. DOI: 10.1152/ajpgi.00537.2010. View