The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure.
Acetaminophen
/ adverse effects
Animals
Blood Platelets
/ immunology
Carbon Tetrachloride
/ adverse effects
Chemical and Drug Induced Liver Injury
/ etiology
Humans
Lectins, C-Type
/ genetics
Liver
/ drug effects
Mice
Mice, Inbred C57BL
Neutrophils
/ immunology
Tumor Necrosis Factor-alpha
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 04 2020
22 04 2020
Historique:
received:
31
05
2018
accepted:
17
03
2020
entrez:
24
4
2020
pubmed:
24
4
2020
medline:
1
8
2020
Statut:
epublish
Résumé
Acetaminophen (APAP) is the main cause of acute liver failure in the West. Specific efficacious therapies for acute liver failure (ALF) are limited and time-dependent. The mechanisms that drive irreversible acute liver failure remain poorly characterized. Here we report that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage after toxic liver injury. Our data demonstrate that blocking platelet CLEC-2 signalling enhances liver recovery from acute toxic liver injuries (APAP and carbon tetrachloride) by increasing tumour necrosis factor-α (TNF-α) production which then enhances reparative hepatic neutrophil recruitment. We provide data from humans and mice demonstrating that platelet CLEC-2 influences the hepatic sterile inflammatory response and that this can be manipulated for therapeutic benefit in acute liver injury. Since CLEC-2 mediated platelet activation is independent of major haemostatic pathways, blocking this pathway represents a coagulopathy-sparing, specific and novel therapy in acute liver failure.
Identifiants
pubmed: 32321925
doi: 10.1038/s41467-020-15584-3
pii: 10.1038/s41467-020-15584-3
pmc: PMC7176690
doi:
Substances chimiques
CLEC-2 protein, mouse
0
Lectins, C-Type
0
Tumor Necrosis Factor-alpha
0
Acetaminophen
362O9ITL9D
Carbon Tetrachloride
CL2T97X0V0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1939Subventions
Organisme : British Heart Foundation
ID : CH/03/003/15571
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15048
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17169
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT100666MA
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Références
Bernal, W. & Wendon, J. Acute liver failure. N. Engl. J. Med. 369, 2525–2534 (2013).
pubmed: 24369077
doi: 10.1056/NEJMra1208937
pmcid: 24369077
Jaeschke, H. Acetaminophen: dose-dependent drug hepatotoxicity and acute liver failure in patients. Dig. Dis. 33, 464–471 (2015).
pubmed: 26159260
pmcid: 4520394
doi: 10.1159/000374090
Bernsmeier, C., Antoniades, C. G. & Wendon, J. What’s new in acute liver failure? Intensive Care Med. 40, 1545–1548 (2014).
pubmed: 24981954
doi: 10.1007/s00134-014-3350-4
pmcid: 24981954
O’Grady, J. Timing and benefit of liver transplantation in acute liver failure. J. Hepatol. 60, 663–670 (2014).
pubmed: 24211740
doi: 10.1016/j.jhep.2013.10.024
pmcid: 24211740
Craig, D. G. et al. Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity. Br. J. Clin. Pharm. 73, 285–294 (2012).
doi: 10.1111/j.1365-2125.2011.04067.x
Krenkel, O., Mossanen, J. C. & Tacke, F. Immune mechanisms in acetaminophen-induced acute liver failure. Hepatobiliary Surg. Nutr. 3, 331–343 (2014).
pubmed: 25568858
pmcid: 4273118
Speiser, J. L., Lee, W. M., Karvellas, C. J. & Group, U. S. A. L. F. S. Predicting outcome on admission and post-admission for acetaminophen-induced acute liver failure using classification and regression tree models. PLoS One 10, e0122929 (2015).
pubmed: 25885260
pmcid: 4401567
doi: 10.1371/journal.pone.0122929
Jaeschke, H., Xie, Y. & McGill, M. R. Acetaminophen-induced liver injury: from animal models to humans. J. Clin. Transl. Hepatol. 2, 153–161 (2014).
pubmed: 26355817
pmcid: 4521247
McGill, M. R. et al. The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J. Clin. Invest. 122, 1574–1583 (2012).
pubmed: 22378043
pmcid: 3314460
doi: 10.1172/JCI59755
Woolbright, B. L. & Jaeschke, H. Sterile inflammation in acute liver injury: myth or mystery? Expert Rev. Gastroenterol. Hepatol. 9, 1027–1029 (2015).
pubmed: 26186639
pmcid: 4613762
doi: 10.1586/17474124.2015.1060855
Basu, S. Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 189, 113–127 (2003).
pubmed: 12821287
doi: 10.1016/S0300-483X(03)00157-4
pmcid: 12821287
Chen, M. et al. High-mobility group box 1 exacerbates CCl(4)-induced acute liver injury in mice. Clin. Immunol. 153, 56–63 (2014).
pubmed: 24726765
doi: 10.1016/j.clim.2014.03.021
pmcid: 24726765
Brenner, C., Galluzzi, L., Kepp, O. & Kroemer, G. Decoding cell death signals in liver inflammation. J. Hepatol. 59, 583–594 (2013).
pubmed: 23567086
doi: 10.1016/j.jhep.2013.03.033
pmcid: 23567086
Kubes, P. & Mehal, W. Z. Sterile inflammation in the liver. Gastroenterology 143, 1158–1172 (2012).
pubmed: 22982943
doi: 10.1053/j.gastro.2012.09.008
pmcid: 22982943
McDonald, B. & Kubes, P. Innate immune cell trafficking and function during sterile inflammation of the liver. Gastroenterology 151, 1087–1095 (2016).
pubmed: 27725145
doi: 10.1053/j.gastro.2016.09.048
pmcid: 27725145
Slaba, I. et al. Imaging the dynamic platelet-neutrophil response in sterile liver injury and repair in mice. Hepatology 62, 1593–1605 (2015).
pubmed: 26202541
doi: 10.1002/hep.28003
pmcid: 26202541
Chauhan, A., Adams, D. H., Watson, S. P. & Lalor, P. F. Platelets: No longer bystanders in liver disease. Hepatology 64, 1774–1784 (2016).
pubmed: 26934463
pmcid: 5082495
doi: 10.1002/hep.28526
Lalor, P. F., Herbert, J., Bicknell, R. & Adams, D. H. Hepatic sinusoidal endothelium avidly binds platelets in an integrin-dependent manner, leading to platelet and endothelial activation and leukocyte recruitment. Am. J. Physiol. Gastrointest. Liver Physiol. 304, G469–G478 (2013).
pubmed: 23257923
doi: 10.1152/ajpgi.00407.2012
pmcid: 23257923
Kwon, H. J., Won, Y. S., Park, O., Feng, D. & Gao, B. Opposing effects of prednisolone treatment on T/NKT cell- and hepatotoxin-mediated hepatitis in mice. Hepatology 59, 1094–1106 (2014).
pubmed: 24115096
pmcid: 3943761
doi: 10.1002/hep.26748
Miyakawa, K. et al. Platelets and protease-activated receptor-4 contribute to acetaminophen-induced liver injury in mice. Blood 126, 1835–1843 (2015).
pubmed: 26179083
pmcid: 4600019
doi: 10.1182/blood-2014-09-598656
Hitchcock, J. R. et al. Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets. J. Clin. Invest 125, 4429–4446 (2015).
pubmed: 26571395
pmcid: 4665792
doi: 10.1172/JCI79070
Kerrigan, A. M. et al. Podoplanin-expressing inflammatory macrophages activate murine platelets via CLEC-2. J. Thromb. Haemost. 10, 484–486 (2012).
pubmed: 22212362
pmcid: 3433653
doi: 10.1111/j.1538-7836.2011.04614.x
Rayes, J. et al. The podoplanin-CLEC-2 axis inhibits inflammation in sepsis. Nat. Commun. 8, 2239 (2017).
pubmed: 29269852
pmcid: 5740111
doi: 10.1038/s41467-017-02402-6
Navarro-Nunez, L., Langan, S. A., Nash, G. B. & Watson, S. P. The physiological and pathophysiological roles of platelet CLEC-2. Thromb. Haemost. 109, 991–998 (2013).
pubmed: 23572154
pmcid: 3693086
doi: 10.1160/TH13-01-0060
Holt, M. P., Cheng, L. & Ju, C. Identification and characterization of infiltrating macrophages in acetaminophen-induced liver injury. J. Leukoc. Biol. 84, 1410–1421 (2008).
pubmed: 18713872
pmcid: 2614594
doi: 10.1189/jlb.0308173
Finney, B. A. et al. CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development. Blood 119, 1747–1756 (2012).
pubmed: 22186994
pmcid: 3351942
doi: 10.1182/blood-2011-09-380709
Nurden, A. T. Platelets, inflammation and tissue regeneration. Thromb. Haemost. 105(Suppl 1), S13–S33 (2011).
pubmed: 21479340
pmcid: 21479340
Ripoche, J. Blood platelets and inflammation: their relationship with liver and digestive diseases. Clin. Res Hepatol. Gastroenterol. 35, 353–357 (2011).
pubmed: 21482218
doi: 10.1016/j.clinre.2011.02.012
pmcid: 21482218
Watson, S. P., Herbert, J. M. & Pollitt, A. Y. GPVI and CLEC-2 in hemostasis and vascular integrity. J. Thromb. Haemost. 8, 1456–1467 (2010).
pubmed: 20345705
doi: 10.1111/j.1538-7836.2010.03875.x
pmcid: 20345705
Lee, R. H. & Bergmeier, W. Platelet immunoreceptor tyrosine-based activation motif (ITAM) and hemITAM signaling and vascular integrity in inflammation and development. J. Thromb. Haemost. 14, 645–654 (2016).
pubmed: 26749528
doi: 10.1111/jth.13250
pmcid: 26749528
Boulaftali, Y., Hess, P. R., Kahn, M. L. & Bergmeier, W. Platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling and vascular integrity. Circ. Res. 114, 1174–1184 (2014).
pubmed: 24677237
pmcid: 4000726
doi: 10.1161/CIRCRESAHA.114.301611
Boulaftali, Y. et al. Platelet ITAM signaling is critical for vascular integrity in inflammation. J. Clin. Invest 123, 908–916 (2013).
pubmed: 23348738
pmcid: 3561801
Hou, T. Z. et al. A distinct subset of podoplanin (gp38) expressing F4/80+ macrophages mediate phagocytosis and are induced following zymosan peritonitis. FEBS Lett. 584, 3955–3961 (2010).
pubmed: 20682314
doi: 10.1016/j.febslet.2010.07.053
pmcid: 20682314
Kasravi, F. B. et al. Bacterial translocation in acute liver injury induced by D-galactosamine. Hepatology 23, 97–103 (1996).
pubmed: 8550055
pmcid: 8550055
Suzuki-Inoue, K. et al. A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2. Blood 107, 542–549 (2006).
pubmed: 16174766
doi: 10.1182/blood-2005-05-1994
pmcid: 16174766
Smith, C. W. et al. TREM-like transcript 1: a more sensitive marker of platelet activation than P-selectin in humans and mice. Blood Adv. 2, 2072–2078 (2018).
pubmed: 30120105
pmcid: 6113608
doi: 10.1182/bloodadvances.2018017756
Amemiya, H., Kono, H. & Fujii, H. Liver regeneration is impaired in macrophage colony stimulating factor deficient mice after partial hepatectomy: the role of M-CSF-induced macrophages. J. Surg. Res. 165, 59–67 (2011).
pubmed: 20031174
doi: 10.1016/j.jss.2009.08.008
Shiratori, Y. et al. Role of macrophages in regeneration of liver. Dig. Dis. Sci. 41, 1939–1946 (1996).
pubmed: 8888704
doi: 10.1007/BF02093593
Nishiyama, K. et al. Mouse CD11b+Kupffer cells recruited from bone marrow accelerate liver regeneration after partial hepatectomy. PLoS One 10, e0136774 (2015).
pubmed: 26333171
pmcid: 4557907
doi: 10.1371/journal.pone.0136774
Akerman, P. et al. Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy. Am. J. Physiol. 263, G579–G585 (1992).
pubmed: 1415718
pmcid: 1415718
Antoniades, C. G., Berry, P. A., Wendon, J. A. & Vergani, D. The importance of immune dysfunction in determining outcome in acute liver failure. J. Hepatol. 49, 845–861 (2008).
pubmed: 18801592
doi: 10.1016/j.jhep.2008.08.009
pmcid: 18801592
Josefsson, E. C., Gebhard, H. H., Stossel, T. P., Hartwig, J. H. & Hoffmeister, K. M. The macrophage alphaMbeta2 integrin alphaM lectin domain mediates the phagocytosis of chilled platelets. J. Biol. Chem. 280, 18025–18032 (2005).
pubmed: 15741160
doi: 10.1074/jbc.M501178200
pmcid: 15741160
Hoffmeister, K. M. et al. The clearance mechanism of chilled blood platelets. Cell 112, 87–97 (2003).
pubmed: 12526796
doi: 10.1016/S0092-8674(02)01253-9
pmcid: 12526796
Acton, S. E. et al. Dendritic cells control fibroblastic reticular network tension and lymph node expansion. Nature 514, 498–502 (2014).
pubmed: 25341788
pmcid: 4235005
doi: 10.1038/nature13814
Ward, L. S. C., et al. Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets. J. Cell Sci. 132, https://doi.org/10.1242/jcs.222067 (2019).
Scull, C. M., Hays, W. D. & Fischer, T. H. Macrophage pro-inflammatory cytokine secretion is enhanced following interaction with autologous platelets. J. Inflamm. (Lond.) 7, 53 (2010).
doi: 10.1186/1476-9255-7-53
Hottz, E. D. et al. Platelet activation and apoptosis modulate monocyte inflammatory responses in dengue. J. Immunol. 193, 1864–1872 (2014).
pubmed: 25015827
pmcid: 4137323
doi: 10.4049/jimmunol.1400091
Mantovani, A. & Garlanda, C. Platelet-macrophage partnership in innate immunity and inflammation. Nat. Immunol. 14, 768–770 (2013).
pubmed: 23867924
doi: 10.1038/ni.2666
pmcid: 23867924
Schwabe, R. F. & Brenner, D. A. Mechanisms of liver injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G583–G589 (2006).
pubmed: 16537970
doi: 10.1152/ajpgi.00422.2005
pmcid: 16537970
Blendis, L. & Dotan, I. Anti-TNF therapy for severe acute alcoholic hepatitis: What went wrong? Gastroenterology 127, 1637–1639 (2004).
pubmed: 15521033
doi: 10.1053/j.gastro.2004.09.089
pmcid: 15521033
Jaeschke, H., Williams, C. D., Ramachandran, A. & Bajt, M. L. Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int. 32, 8–20 (2012).
pubmed: 21745276
doi: 10.1111/j.1478-3231.2011.02501.x
pmcid: 21745276
Liu, Z. X., Han, D., Gunawan, B. & Kaplowitz, N. Neutrophil depletion protects against murine acetaminophen hepatotoxicity. Hepatology 43, 1220–1230 (2006).
pubmed: 16729305
doi: 10.1002/hep.21175
pmcid: 16729305
Marques, P. E. et al. Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure. Hepatology 56, 1971–1982 (2012).
pubmed: 22532075
doi: 10.1002/hep.25801
pmcid: 22532075
Jaeschke, H. & Liu, J. Neutrophil depletion protects against murine acetaminophen hepatotoxicity: another perspective. Hepatology 45, 1588–1589 (2007). author reply 1589.
pubmed: 17539019
doi: 10.1002/hep.21549
pmcid: 17539019
Cover, C. et al. Pathophysiological role of the acute inflammatory response during acetaminophen hepatotoxicity. Toxicol. Appl. Pharm. 216, 98–107 (2006).
doi: 10.1016/j.taap.2006.04.010
Hou, H. S. et al. Deficiency of interleukin-15 enhances susceptibility to acetaminophen-induced liver injury in mice. PLoS One 7, e44880 (2012).
pubmed: 23028657
pmcid: 3445599
doi: 10.1371/journal.pone.0044880
Williams, C. D., Bajt, M. L., Farhood, A. & Jaeschke, H. Acetaminophen-induced hepatic neutrophil accumulation and inflammatory liver injury in CD18-deficient mice. Liver Int. 30, 1280–1292 (2010).
pubmed: 20500806
pmcid: 4278356
doi: 10.1111/j.1478-3231.2010.02284.x
Williams, C. D. et al. Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and humans. Toxicol. Appl. Pharm. 275, 122–133 (2014).
doi: 10.1016/j.taap.2014.01.004
Yang, W. et al. Neutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair. Nat. Commun. 10, 1076 (2019).
pubmed: 30842418
pmcid: 6403250
doi: 10.1038/s41467-019-09046-8
Jimenez Calvente, C., et al. Neutrophils contribute to spontaneous resolution of liver inflammation and fibrosis via microRNA-223. J. Clin. Invest. 130, 4091–4109(2019).
Wright, H. L., Moots, R. J., Bucknall, R. C. & Edwards, S. W. Neutrophil function in inflammation and inflammatory diseases. Rheumatol. (Oxf.) 49, 1618–1631 (2010).
doi: 10.1093/rheumatology/keq045
Wang, J. et al. Visualizing the function and fate of neutrophils in sterile injury and repair. Science 358, 111–116 (2017).
pubmed: 28983053
doi: 10.1126/science.aam9690
pmcid: 28983053
Dhanda, A. D. & Collins, P. L. Immune dysfunction in acute alcoholic hepatitis. World J. Gastroenterol. 21, 11904–11913 (2015).
pubmed: 26576079
pmcid: 4641112
doi: 10.3748/wjg.v21.i42.11904
Taylor, N. J. et al. Circulating neutrophil dysfunction in acute liver failure. Hepatology 57, 1142–1152 (2013).
pubmed: 23079896
doi: 10.1002/hep.26102
pmcid: 23079896
Irvine, K. M., Ratnasekera, I., Powell, E. E. & Hume, D. A. Causes and consequences of innate immune dysfunction in cirrhosis. Front Immunol. 10, 293 (2019).
pubmed: 30873165
pmcid: 6401613
doi: 10.3389/fimmu.2019.00293
Zhang, L. et al. Granulocyte colony-stimulating factor treatment ameliorates liver injury and improves survival in rats with D-galactosamine-induced acute liver failure. Toxicol. Lett. 204, 92–99 (2011).
pubmed: 21550386
doi: 10.1016/j.toxlet.2011.04.016
pmcid: 21550386
Moreau, R. & Rautou, P. E. G-CSF therapy for severe alcoholic hepatitis: targeting liver regeneration or neutrophil function? Am. J. Gastroenterol. 109, 1424–1426 (2014).
pubmed: 25196873
doi: 10.1038/ajg.2014.250
pmcid: 25196873
Lisman, T. Platelet-neutrophil interactions as drivers of inflammatory and thrombotic disease. Cell Tissue Res. 371, 567–576 (2018).
pubmed: 29178039
doi: 10.1007/s00441-017-2727-4
pmcid: 29178039
Zhao, X. et al. TNF signaling drives myeloid-derived suppressor cell accumulation. J. Clin. Invest. 122, 4094–4104 (2012).
pubmed: 23064360
pmcid: 3484453
doi: 10.1172/JCI64115
Zhang, H. et al. The critical role of myeloid-derived suppressor cells and FXR activation in immune-mediated liver injury. J. Autoimmun. 53, 55–66 (2014).
pubmed: 24721598
doi: 10.1016/j.jaut.2014.02.010
pmcid: 24721598
Li, S. et al. Expansion of granulocytic, myeloid-derived suppressor cells in response to ethanol-induced acute liver damage. Front Immunol. 9, 1524 (2018).
pubmed: 30072984
pmcid: 6060237
doi: 10.3389/fimmu.2018.01524
Li, P. Z., Li, J. Z., Li, M., Gong, J. P. & He, K. An efficient method to isolate and culture mouse Kupffer cells. Immunol. Lett. 158, 52–56 (2014).
pubmed: 24333337
doi: 10.1016/j.imlet.2013.12.002
pmcid: 24333337