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Journal of Inflammation

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Open Access 01-12-2018 | Research

Plasma vascular non-inflammatory molecule 3 is associated with gastrointestinal acute graft-versus-host disease in mice

Authors: Na Wang, Xiaoyi Qin, Yigeng Cao, Bin Liang, Kang Yu, Haige Ye

Published in: Journal of Inflammation | Issue 1/2018

Abstract

Background

Gastrointestinal acute graft-versus-host disease (GI aGVHD) is a lethal complication following allogeneic hematopoietic stem cell transplantation (HSCT). However, it is still very difficult to make a diagnosis of GI aGVHD in practice. To date, no consensus plasma biomarker of GI aGVHD can be used to help make a diagnosis. Here, we attempted to identify GI aGVHD associated plasma proteins in murine model, which can help make a diagnosis of GI aGVHD.

Methods

We used 8-plex isobaric tags for relative and absolute quantitation (8-plex iTRAQ) to screen out proteins in plasma samples taken from murine models before and after allogeneic HSCT. Next mRNA expressions were validated by quantitative real-time polymerase chain reaction in mouse intestinal epithelial samples.

Results

We found that five proteins were increased at least 2-fold in the allogeneic group at day 7 compared with days 0, 3 and 15 (after Cyclosporin A treatment) and the syngeneic group at day 7. These 5 proteins were VNN3, ZNF746, C4BP, KNG1 and FETUB, and they were consistent with results from negative labeling with 8-plex iTRAQ. Furthermore, increase in mRNA level of VNN3 was confirmed in murine intestinal epithelial samples with aGVHD.

Conclusions

Our results demonstrate that plasma VNN3 protein is associated with GI aGVHD in murine model.

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Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, Martin PJ, Sandmaier BM, Marr KA, Appelbaum FR, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101.CrossRefPubMedPubMedCentral

Martin PJ, McDonald GB, Sanders JE, Anasetti C, Appelbaum FR, Deeg HJ, Nash RA, Petersdorf EW, Hansen JA, Storb R. Increasingly frequent diagnosis of acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2004;10:320–7.CrossRefPubMed

Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009;373:1550–61.CrossRefPubMedPubMedCentral

Kambham N, Higgins JP, Sundram U, Troxell ML. Hematopoietic stem cell transplantation: graft versus host disease and pathology of gastrointestinal tract, liver, and lung. Adv Anat Pathol. 2014;21:301–20.CrossRefPubMed

Snover DC. Mucosal damage simulating acute graft-versus-host reaction in cytomegalovirus colitis. Transplantation. 1985;39:669–70.CrossRefPubMed

Parfitt JR, Jayakumar S, Driman DK. Mycophenolate mofetil-related gastrointestinal mucosal injury: variable injury patterns, including graft-versus-host disease-like changes. Am J Surg Pathol. 2008;32:1367–72.CrossRefPubMed

Lorenz F, Marklund S, Werner M, Palmqvist R, Wahlin BE, Wahlin A. Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation. Sci Rep. 2015;5:7920.CrossRefPubMedPubMedCentral

McDonald GB, Tabellini L, Storer BE, Lawler RL, Martin PJ, Hansen JA. Plasma biomarkers of acute GVHD and nonrelapse mortality: predictive value of measurements before GVHD onset and treatment. Blood. 2015;126:113–20.CrossRefPubMedPubMedCentral

Ferrara JL, Harris AC, Greenson JK, Braun TM, Holler E, Teshima T, Levine JE, Choi SW, Huber E, Landfried K, et al. Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood. 2011;118:6702–8.CrossRefPubMedPubMedCentral

10.

Ye H, Sun L, Huang X, Zhang P, Zhao X. A proteomic approach for plasma biomarker discovery with 8-plex iTRAQ labeling and SCX-LC-MS/MS. Mol Cell Biochem. 2010;343:91–9.CrossRefPubMed

11.

Lin Y, Hu X, Cheng H, Pang Y, Wang L, Zou L, Xu S, Zhuang X, Jiang C, Yuan W, et al. Graft-versus-host disease causes broad suppression of hematopoietic primitive cells and blocks megakaryocyte differentiation in a murine model. Biol Blood Marrow Transplant. 2014;20:1290–300.CrossRefPubMed

12.

Iwasaki T, Hamano T, Saheki K, Kuroiwa T, Kataoka Y, Takemoto Y, Ogata A, Sugihara A, Terada N, Fujimoto J, Kakishita E. Effect of graft-versus-host disease (GVHD) on host hematopoietic progenitor cells is mediated by Fas-Fas ligand interactions but this does not explain the effect of GVHD on donor cells. Cell Immunol. 1999;197:30–8.CrossRefPubMed

13.

Pan B, Zeng L, Cheng H, Song G, Chen C, Zhang Y, Li Z, Xu K. Altered balance between Th1 and Th17 cells in circulation is an indicator for the severity of murine acute GVHD. Immunol Lett. 2012;142:48–54.CrossRefPubMed

14.

Pan B, Zhang Y, Sun Y, Cheng H, Wu Y, Song G, Chen W, Zeng L, Xu K. Deviated balance between Th1 and Th17 cells exacerbates acute graft-versus-host disease in mice. Cytokine. 2014;68:69–75.CrossRefPubMed

15.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25:402–8.CrossRefPubMed

16.

Penack O, Holler E, van den Brink MR. Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors. Blood. 2010;115:1865–72.CrossRefPubMed

17.

Zhang L, Chu J, Yu J, Wei W. Cellular and molecular mechanisms in graft-versus-host disease. J Leukoc Biol. 2016;99:279–87.CrossRefPubMed

18.

Ferrara JL, Deeg HJ. Graft-versus-host disease. N Engl J Med. 1991;324:667–74.CrossRefPubMed

19.

Bouchal P, Roumeliotis T, Hrstka R, Nenutil R, Vojtesek B, Garbis SD. Biomarker discovery in low-grade breast cancer using isobaric stable isotope tags and two-dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2DLC-MS/MS) based quantitative proteomic analysis. J Proteome Res. 2009;8:362–73.CrossRefPubMed

20.

Lin ZY, Chuang WL. Pharmacologic concentrations of ascorbic acid cause diverse influence on differential expressions of angiogenic chemokine genes in different hepatocellular carcinoma cell lines. Biomed Pharmacother. 2010;64:348–51.CrossRefPubMed

21.

Martin F, Malergue F, Pitari G, Philippe JM, Philips S, Chabret C, Granjeaud S, Mattei MG, Mungall AJ, Naquet P, Galland F. Vanin genes are clustered (human 6q22-24 and mouse 10A2B1) and encode isoforms of pantetheinase ectoenzymes. Immunogenetics. 2001;53:296–306.CrossRefPubMed

22.

Nitto T, Inoue T, Node K. Alternative spliced variants in the pantetheinase family of genes expressed in human neutrophils. Gene. 2008;426:57–64.CrossRefPubMed

23.

Jansen PA, Kamsteeg M, Rodijk-Olthuis D, van Vlijmen-Willems IM, de Jongh GJ, Bergers M, Tjabringa GS, Zeeuwen PL, Schalkwijk J. Expression of the vanin gene family in normal and inflamed human skin: induction by proinflammatory cytokines. J Invest Dermatol. 2009;129:2167–74.CrossRefPubMed

24.

Beauvillain C, Cunin P, Doni A, Scotet M, Jaillon S, Loiry ML, Magistrelli G, Masternak K, Chevailler A, Delneste Y, Jeannin P. CCR7 is involved in the migration of neutrophils to lymph nodes. Blood. 2011;117:1196–204.CrossRefPubMed

25.

Scozzi D, Ibrahim M, Menna C, Krupnick AS, Kreisel D, Gelman AE. The role of Neutrophils in transplanted organs. Am J Transplant. 2017;17:328–35.CrossRefPubMed

26.

Hill GR, Ferrara JL. The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation. Blood. 2000;95:2754–9.PubMed

27.

Ye H, Lv M, Zhao X, Zhao X, Huang X. Plasma level of lipopolysaccharide-binding protein is indicative of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2012;95:680–8.CrossRefPubMed

28.

Nogueira-Machado JA, de Oliveira Volpe CM. HMGB-1 as a target for inflammation controlling. Recent Pat Endocr Metab Immune Drug Discov. 2012;6:201–9.CrossRefPubMed

29.

Yumoto M, Nishida O, Moriyama K, Shimomura Y, Nakamura T, Kuriyama N, Hara Y, Yamada S. In vitro evaluation of high mobility group box 1 protein removal with various membranes for continuous hemofiltration. Ther Apher Dial. 2011;15:385–93.CrossRefPubMed

30.

Amer J, Weiss L, Reich S, Shapira MY, Slavin S, Fibach E. The oxidative status of blood cells in a murine model of graft-versus-host disease. Ann Hematol. 2007;86:753–8.CrossRefPubMed

31.

Manzanillo PS, Ayres JS, Watson RO, Collins AC, Souza G, Rae CS, Schneider DS, Nakamura K, Shiloh MU, Cox JS. The ubiquitin ligase parkin mediates resistance to intracellular pathogens. Nature. 2013;501:512–6.CrossRefPubMedPubMedCentral

32.

Konya V, Mjosberg J. Innate lymphoid cells in graft-versus-host disease. Am J Transplant. 2015;15:2795–801.CrossRefPubMedPubMedCentral

33.

Hofmeyer T, Schmelz S, Degiacomi MT, Dal Peraro M, Daneschdar M, Scrima A, van den Heuvel J, Heinz DW, Kolmar H. Arranged sevenfold: structural insights into the C-terminal oligomerization domain of human C4b-binding protein. J Mol Biol. 2013;425:1302–17.CrossRefPubMed

34.

Zhang K, Huang XZ, Li XN, Feng M, Li L, Cai XJ, Zhang C, Liu XL, Zhang MX, Zhang Y, et al. Interleukin 6 destabilizes atherosclerotic plaques by downregulating prolyl-4-hydroxylase alpha1 via a mitogen-activated protein kinase and c-Jun pathway. Arch Biochem Biophys. 2012;528:127–33.CrossRefPubMed

35.

Morris ES, Hill GR. Advances in the understanding of acute graft-versus-host disease. Br J Haematol. 2007;137:3–19.CrossRefPubMed

36.

Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Unemori EN, Lark MW, Amento E, Libby P. Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res. 1994;75:181–9.CrossRefPubMed

37.

Isordia-Salas I, Pixley RA, Sainz IM, Martinez-Murillo C, Colman RW. The role of plasma high molecular weight kininogen in experimental intestinal and systemic inflammation. Arch Med Res. 2005;36:87–95.CrossRefPubMed

38.

Klambt V, Wohlfeil SA, Schwab L, Hulsdunker J, Ayata K, Apostolova P, Schmitt-Graeff A, Dierbach H, Prinz G, Follo M, et al. A novel function for P2Y2 in myeloid recipient-derived cells during graft-versus-host disease. J Immunol. 2015;195:5795–804.CrossRefPubMed

39.

Socie G, Mary JY, Lemann M, Daneshpouy M, Guardiola P, Meignin V, Ades L, Esperou H, Ribaud P, Devergie A, et al. Prognostic value of apoptotic cells and infiltrating neutrophils in graft-versus-host disease of the gastrointestinal tract in humans: TNF and Fas expression. Blood. 2004;103:50–7.CrossRefPubMed

40.

Giroux M, Delisle JS, Gauthier SD, Heinonen KM, Hinsinger J, Houde B, Gaboury L, Brochu S, Wu J, Hebert MJ, Perreault C. SMAD3 prevents graft-versus-host disease by restraining Th1 differentiation and granulocyte-mediated tissue damage. Blood. 2011;117:1734–44.CrossRefPubMed

41.

Schwab L, Goroncy L, Palaniyandi S, Gautam S, Triantafyllopoulou A, Mocsai A, Reichardt W, Karlsson FJ, Radhakrishnan SV, Hanke K, et al. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med. 2014;20:648–54.CrossRefPubMed

42.

Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, Wang CR, Schumacker PT, Licht JD, Perlman H, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity. 2013;38:225–36.CrossRefPubMedPubMedCentral

Title: Plasma vascular non-inflammatory molecule 3 is associated with gastrointestinal acute graft-versus-host disease in mice
Authors: Na Wang
Xiaoyi Qin
Yigeng Cao
Bin Liang
Kang Yu
Haige Ye
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Inflammation / Issue 1/2018
Electronic ISSN: 1476-9255
DOI: https://doi.org/10.1186/s12950-017-0178-z

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