Initial proteomic characterization of IMMODIN, commercially available dialysable leukocytes extract

Zuniga-Navarrete, Fernando; Zavala-Meneses, Sofia Guadalupe; Zelnik, Vladimir; Kopacek, Juraj; Skultety, Ludovit

doi:10.1007/s11696-020-01467-w

Original Paper
Published: 05 January 2021

Initial proteomic characterization of IMMODIN, commercially available dialysable leukocytes extract

Fernando Zuniga-Navarrete¹^na1,
Sofia Guadalupe Zavala-Meneses²^na1,
Vladimir Zelnik¹,
Juraj Kopacek¹ &
Ludovit Skultety ORCID: orcid.org/0000-0002-9830-6459^1,2

Chemical Papers volume 75, pages 1959–1968 (2021)Cite this article

139 Accesses
1 Citations
Metrics details

Abstract

One of the most significant public health challenges of the twenty-first century is the prevention and treatment of infectious diseases caused by various microorganisms, including resistant bacteria and viruses. With aging, there is a progressive alteration of the immune system and its responses that may result in immune senescence and immunodepression. Nevertheless, immune modulators can speed up recovery. IMMODIN^® is a commercially available dialysable leukocyte extract prepared from disintegrated white blood cells of healthy human donors. It is used clinically as a prophylactic or therapeutic agent when cell-mediated immunity plays a key role. This initial proteomic study was aiming to evaluate the polypeptide repertoire present in this immunologic preparation. Using our approach, we identified forty-eight unique proteins associated with blood cells or plasma. From them, twenty-eight were detected in at least two independent analyses of three IMMODIN^® preparations. The highest number of proteins was related to innate immunity. There were identified receptors for parasites or microbes that have the ability to recognize the invaders and initiate their inhibition or elimination. We also detected proteins associated with inflammatory response, including those having the potential to inhibit cytokines and treat the cytokine storm. There were found even proteins that can speed up recovery by regulating cell growth and repair.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

References

Alves CH, Boon N, Mulder AA, Koster AJ, Jost CR, Wijnholds J (2019) CRB2 Loss in rod photoreceptors is associated with progressive loss of retinal contrast sensitivity. Int J Mol Sci 20:4069. https://doi.org/10.3390/ijms20174069
CAS Article PubMed Central Google Scholar
Arnaudov A, Kostova Z (2015) Dialysable leukocyte extracts in immunotherapy. Biotechnol Biotechnol Equip 29:1017–1023. https://doi.org/10.1080/13102818.2015.1060136
CAS Article Google Scholar
Ascher MS, Gottlieb AA, Kirkpatrick CH (eds) (1976) Transfer factor: basic properties and clinical applications. Academic Press Inc., New York, San Francisco, London
Google Scholar
Blann A (2003) The adhesion molecule P-selectin and cardiovascular disease. Eur Heart J 24:2166–2179. https://doi.org/10.1016/j.ehj.2003.08.021
CAS Article PubMed Google Scholar
Bullock WE, Fields JP, Brandriss MW (1972) An Evaluation of transfer factor as immunotherapy for patients with lepromatous leprosy. N Engl J Med 287:1053–1059. https://doi.org/10.1056/NEJM197211232872101
CAS Article PubMed Google Scholar
Burstein E, Hoberg JE, Wilkinson AS, Rumble JM, Csomos RA, Komarck CM, Maine GN, Wilkinson JC, Mayo MW, Duckett CS (2005) COMMD proteins, a novel family of structural and functional homologs of MURR1. J Biol Chem 280:22222–22232. https://doi.org/10.1074/jbc.M501928200
CAS Article PubMed Google Scholar
Cardoso FM, Tomkova M, Petrovajova D, Bubanova M, Ragac O, Hornakova T (2017) New and cost effective cell-based assay for dialyzed leukocyte extract (DLE)-induced Jurkat cells proliferation under azathioprine treatment. J Pharm Biomed Anal 138:100–108. https://doi.org/10.1016/j.jpba.2017.01.052
CAS Article PubMed Google Scholar
Castillo-Briceño Patricia P, Bihan D, Nilges M, Hamaia S, Meseguer J, García-Ayala A, Farndale RW, Mulero V (2011) A role for specific collagen motifs during wound healing and inflammatory response of fibroblasts in the teleost fish gilthead seabream. Mol Immunol 48:826–834. https://doi.org/10.1016/j.molimm.2010.12.004
CAS Article PubMed PubMed Central Google Scholar
Chavakis T, Santoso S, Clemetson KJ, Sachs UJH, Isordia-Salas I, Pixley RA, Nawroth PP, Colman RW, Preissner KT (2003) High molecular weight kininogen regulates platelet-leukocyte interactions by bridging mac-1 and glycoprotein Ib. J Biol Chem 278:45375–45381. https://doi.org/10.1074/jbc.M304344200
CAS Article PubMed Google Scholar
Chen L, Madura K (2005) Increased proteasome activity, ubiquitin-conjugating enzymes, and eEF1A translation factor detected in breast cancer tissue. Cancer Res 65(13):5599–5606. https://doi.org/10.1158/0008-5472.CAN-05-0201
CAS Article PubMed Google Scholar
Cherenko SO, Reva OA, Rekalova OM, Kibizova NI, Yasir SG, Matvienko YO (2013) Immunotherapy with leukocyte immunomodulator dialysate in patients with multidrug-resistant tuberculosis. Asthma Allerg 3:13–20
Google Scholar
De Fougerolles AR, Sprague AG, Nickerson-Nutter CL, Chi-Rosso G, Rennert PD, Gardner H, Gotwals PJ, Lobb RR, Koteliansky VE (2000) Regulation of inflammation by collagen-binding integrins α1β1 and α2β1 in models of hypersensitivity and arthritis. J Clin Invest 105:721–729. https://doi.org/10.1172/JCI7911
Article PubMed PubMed Central Google Scholar
Delgado O, Romano EL, Belfort E, Pifano F, Scorza JV, Rojas Z (1981) Dialyzable leukocyte extract therapy in immunodepressed patients with cutaneous leishmaniasis. Clin Immunol Immunopathol 19:351–359. https://doi.org/10.1016/0090-1229(81)90078-7
CAS Article PubMed Google Scholar
Demečková V, Solár P, Hrčková G, Mudroňová D, Bojková B, Kassayová M, Gancarčiková S (2017) Immodin and its immune system supportive role in paclitaxel therapy of 4T1 mouse breast cancer. Biomed Pharmacother 89:245–256. https://doi.org/10.1016/j.biopha.2017.02.034
CAS Article PubMed Google Scholar
Desai A, Grolleau-Julius A, Yung R (2010) Leukocyte function in the aging immune system. J Leukoc Biol 87:1001–1009. https://doi.org/10.1189/jlb.0809542
CAS Article PubMed PubMed Central Google Scholar
Devallire J, Charreau B (2011) The adaptor Lnk (SH2B3): An emerging regulator in vascular cells and a link between immune and inflammatory signaling. Biochem Pharmacol 82(10):1391–1402. https://doi.org/10.1016/j.bcp.2011.06.023
CAS Article Google Scholar
Doelker I, Anderer FA (1992) The CySF-L2 factor from dialysable human leucocyte extract activates natural killer cytotoxicity by induction of interferon γ. Cancer Immunol Immunother 34:299–305. https://doi.org/10.1007/BF01741550
CAS Article PubMed Google Scholar
Estrada-Parra S, Chavez-Sanchez R, Ondarza-Aguilera R, Correa-Meza B, Serrano-Miranda E, Monges-Nicolau A, Calva-Pellicer C (1995) Immunotherapy with transfer factor of recurrent herpes simplex type I. Arch Med Res 26:S87-92
PubMed Google Scholar
Estrada-Parra S, Nagaya A, Serrano E, Rodriguez O, Santamaria V, Ondarza R, Chavez R, Correa B, Monges A, Cabezas R, Calva C, Estrada-Garcia I (1998) Comparative study of transfer factor and acyclovir in the treatment of herpes zoster. Int J Immunopharmacol 20:521–535. https://doi.org/10.1016/S0192-0561(98)00031-9
CAS Article PubMed Google Scholar
Fedoseienko A, Wijers M, Wolters JC, Dekker D, Smit M, Huijkman N, Kloosterhuis N, Klug H, Schepers A, Van Dijk KW, Levels JHM, Billadeau DD, Hofker MH, Van Deursen J, Westerterp M, Burstein E, Kuivenhoven JA, Van De Sluis B (2018) The COMMD family regulates plasma LDL levels and attenuates atherosclerosis through stabilizing the CCC complex in endosomal LDLR traffcking. Circ Res 122:1648–1660. https://doi.org/10.1161/CIRCRESAHA.117.312004
CAS Article PubMed Google Scholar
Gasteiger G, D’osualdo A, Schubert DA, Weber A, Bruscia EM, Hartl D, (2017) Cellular Innate Immunity: An Old Game with New Players. J Innate Immun 9:111–125. https://doi.org/10.1159/000453397
CAS Article PubMed Google Scholar
Gatlin CL, Eng JK, Cross ST, Detter JC, Yates JR (2000) Automated identification of amino acid sequence variations in proteins by HPLC/microspray tandem mass spectrometry. Anal Chem 72:757–763. https://doi.org/10.1021/ac991025n
CAS Article PubMed Google Scholar
Gómez-Moutón C, Mañes S (2007) Establishment and maintenance of cell polarity during leukocyte chemotaxis. Cell Adh Migr 1:69–76. https://doi.org/10.4161/cam.1.2.4547
Article PubMed PubMed Central Google Scholar
Hamprecht KH, Vötsch W, Anderer FA (1989) A dialysable acid factor from human leukocyte extracts activates tumor cell lysis mediated by human monocytes and natural killer cells. Oncol Res Treat 12:120–127. https://doi.org/10.1159/000216618
CAS Article Google Scholar
Hannappel E (2007) β-thymosins. Ann N Y Acad Sci 1112:21–37. https://doi.org/10.1196/annals.1415.018
CAS Article PubMed Google Scholar
Happel N, Doenecke D (2009) Histone H1 and its isoforms: Contribution to chromatin structure and function. Gene 431:1–12. https://doi.org/10.1016/j.gene.2008.11.003
CAS Article PubMed Google Scholar
Hernández-Esquivel MA, Pérez-Torres A, Romero-Romero L, Reyes-Matute A, Loaiza B, Mellado-Sánchez G, Pavón L, Medina-Rivero E, Pestell RG, Pérez-Tapia SM, Velasco-Velázquez MA (2018) The dialyzable leukocyte extract TransferonTM inhibits tumor growth and brain metastasis in a murine model of prostate cancer. Biomed Pharmacother 101:938–944. https://doi.org/10.1016/j.biopha.2018.03.012
CAS Article PubMed Google Scholar
Howe J, Richter W, Hawkins L, Rossle M, Alexander C, Fournier K, Mach J, Waelli T, Gorczynski R, Ulmer A, Brade H, Zamyatina A, Kosma P, Rietschel ET, Brandenburg K (2008) Hemoglobin enhances the biological activity of synthetic and natural bacterial (endotoxic) virulence factors: a general principle. Med Chem (Los Angeles) 4:520–525. https://doi.org/10.2174/157340608786242089
CAS Article Google Scholar
Ishida I, Kumanogoh A, Suzuki K, Akahani S, Noda K, Kikutani H (2003) Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: Implications for the regulation of immune and inflammatory responses. Int Immunol 15:1027–1034. https://doi.org/10.1093/intimm/dxg098
CAS Article PubMed Google Scholar
Ito Y, Oinuma I, Katoh H, Kaibuchi K, Negishi M (2006) Sema4D/plexin-B1 activates GSK-3β through R-Ras GAP activity, inducing growth cone collapse. EMBO Rep 7:704–709. https://doi.org/10.1038/sj.embor.7400737
CAS Article PubMed PubMed Central Google Scholar
Izquierdo-Bouldstridge A, Bustillos A, Bonet-Costa C, Aribau-Miralbés P, García-Gomis D, Dabad M, Esteve-Codina A, Pascual-Reguant L, Peiró S, Esteller M, Murtha M, Millán-Ariño L, Jordan A (2017) Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats. Nucleic Acids Res 45:11622–11642. https://doi.org/10.1093/nar/gkx746
CAS Article PubMed PubMed Central Google Scholar
Izzo A, Kamieniarz K, Schneider R (2008) The histone H1 family: Specific members, specific functions? Biol Chem 389:333–343. https://doi.org/10.1515/BC.2008.037
CAS Article PubMed Google Scholar
Jakobsson L, Bentley K, Gerhardt H (2009) VEGFRs and Notch: A dynamic collaboration in vascular patterning. Biochem Soc Trans 37:1233–1236. https://doi.org/10.1042/BST0371233
CAS Article PubMed Google Scholar
Jambou R, Combes V, Jambou M-J, Weksler BB, Couraud P-O, Grau GE (2010) Plasmodium falciparum adhesion on human brain microvascular endothelial cells involves transmigration-like cup formation and induces opening of intercellular junctions. PLoS Pathog 6:e1001021. https://doi.org/10.1371/journal.ppat.1001021
CAS Article PubMed PubMed Central Google Scholar
Jaskiewicz E, Jodłowska M, Kaczmarek R, Zerka A (2019) Erythrocyte glycophorins as receptors for Plasmodium merozoites. Parasites Vectors. https://doi.org/10.1186/s13071-019-3575-8
Article PubMed PubMed Central Google Scholar
Kirkpatrick CH (2000) Transfer factors: identification of conserved sequences in transfer factor molecules. Mol Med 6:332–341. https://doi.org/10.1007/bf03401941
CAS Article PubMed PubMed Central Google Scholar
Kirkpatrick CH, Burger DR, Lawrence HS (eds) (1983) Immunobiology of Transfer Factor. Academic Press Inc, New York
Google Scholar
Klug A (2010) The discovery of zinc fingers and their applications in gene regulation and genome manipulation. Annu Rev Biochem 79:213–231. https://doi.org/10.1146/annurev-biochem-010909-095056
CAS Article PubMed Google Scholar
Knott GJ, Bond CS, Fox AH (2016) The DBHS proteins SFPQ, NONO and PSPC1: A multipurpose molecular scaffold. Nucleic Acids Res 44:3989–4004. https://doi.org/10.1093/nar/gkw271
CAS Article PubMed PubMed Central Google Scholar
Kobayashi H, Yu Y, Volk DE (2019) Thymosins. In: Litwack G (ed) Hormonal Signaling in Biology and Medicine: Comprehensive Modern Endocrinology. Academic Press Inc., New York, pp. 311–326. https://doi.org/10.1016/B978-0-12-813814-4.00013-4
Kusumoto Y, Okuyama H, Shibata T, Konno K, Takemoto Y, Maekawa D, Kononaga T, Ishii T, Akashi-Takamura S, Saitoh S, ichiroh, Ikebuchi R, Moriya T, Ueda M, Miyake K, Ono S, Tomura M, (2018) Epithelial membrane protein 3 (Emp3) downregulates induction and function of cytotoxic T lymphocytes by macrophages via TNF-α production. Cell Immunol 324:33–41. https://doi.org/10.1016/j.cellimm.2017.12.001
CAS Article PubMed Google Scholar
Lai KMV, Pawson T (2000) The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo. Genes Dev 14:1132–1145. https://doi.org/10.1101/gad.14.9.1132
CAS Article PubMed PubMed Central Google Scholar
Lara HH, Turrent LI, Garza-Treviño EN, Tamez-Guerra R, Rodriguez-Padilla C (2010) Clinical and immunological assessment in breast cancer patients receiving anticancer therapy and bovine dialyzable leukocyte extract as an adjuvant. Exp Ther Med 1:425–431. https://doi.org/10.3892/etm_00000066
CAS Article PubMed PubMed Central Google Scholar
Lawrence HS, Borkowsky W (1983) A new basis for the immunoregulatory activities of transfer factor-An arcane dialect in the language of cells. Cell Immunol 82:102–116. https://doi.org/10.1016/0008-8749(83)90145-4
CAS Article PubMed Google Scholar
Li H, Koo Y, Mao X, Sifuentes-Dominguez L, Morris LL, Jia D, Miyata N, Faulkner RA, van Deursen JM, Vooijs M, Billadeau DD, Van de Sluis B, Cleaver O, Burstein E (2015) Endosomal sorting of notch receptors through COM MD9-dependent pathways modulates notch signaling. J Cell Biol 211:605–617. https://doi.org/10.1083/jcb.201505108
CAS Article PubMed PubMed Central Google Scholar
Liepke C, Baxmann S, Heine C, Breithaupt N, Ständker L, Forssmann WG (2003) Human hemoglobin-derived peptides exhibit antimicrobial activity: A class of host defense peptides. J Chromatogr B Anal Technol Biomed Life Sci 791:345–356. https://doi.org/10.1016/S1570-0232(03)00245-9
CAS Article Google Scholar
Lodoen MB, Lanier LL (2006) Natural killer cells as an initial defense against pathogens. Curr Opin Immunol 18:391–398. https://doi.org/10.1016/j.coi.2006.05.002
CAS Article PubMed PubMed Central Google Scholar
Lunin SM, Novoselova EG (2010) Thymus hormones as prospective anti-inflammatory agents. Expert Opin Ther Targets 14:775–786. https://doi.org/10.1517/14728222.2010.499127
CAS Article PubMed Google Scholar
Mačák-Kubašková T, Mudroňová D, Velebný S, Hrčková G (2018) The utilisation of human dialyzable leukocyte extract (IMMODIN) as adjuvant in albendazole therapy on mouse model of larval cestode infection: Immunomodulatory and hepatoprotective effects. Int Immunopharmacol 65:148–158. https://doi.org/10.1016/j.intimp.2018.09.045
CAS Article PubMed Google Scholar
Merkulov S, Zhang WM, Komar AA, Schmaier AH, Barnes E, Zhou Y, Lu X, Iwaki T, Castellino FJ, Luo G, McCrae KR (2008) Deletion of murine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosis. Blood 111:1274–1281. https://doi.org/10.1182/blood-2007-06-092338
CAS Article PubMed PubMed Central Google Scholar
Moir RD, Lathe R, Tanzi RE (2018) The antimicrobial protection hypothesis of Alzheimer’s disease. Alzheimer’s Dement 14:1602–1614. https://doi.org/10.1016/j.jalz.2018.06.3040
Article Google Scholar
Morchikh M, Cribier A, Raffel R, Amraoui S, Cau J, Severac D, Dubois E, Schwartz O, Bennasser Y, Benkirane M (2017) HEXIM1 and NEAT1 long non-coding RNA form a multi-subunit complex that regulates DNA-mediated innate immune response. Mol Cell 67:387-399.e5. https://doi.org/10.1016/j.molcel.2017.06.020
CAS Article PubMed Google Scholar
Pekarek J, Cech K, Barnet K (1991) The clinical use of specific transfer factor. In: Fujisawa T, Sasakawa S, Iicura I, Komatsu F, Yamaguchi Y (eds) Recent advances in transfer factor and dialysable leukocyte extracts. Maruzen, Tokyo, pp 256–263
Google Scholar
Porter SR, Czaplicki G, Mainil J, Guattéo R, Saegerman C (2011) Q fever: current state of knowledge and perspectives of research of a neglected zoonosis. Int J Microbiol 2011:1–22. https://doi.org/10.1155/2011/248418
Article Google Scholar
Prall TM, Graham ME, Karl JA, Wiseman RW, Ericsen AJ, Raveendran M, Alan Harris R, Muzny DM, Gibbs RA, Rogers J, O’Connor DH (2017) Improved full-length killer cell immunoglobulin-like receptor transcript discovery in Mauritian cynomolgus macaques. Immunogenetics 69:325–339. https://doi.org/10.1007/s00251-017-0977-7
CAS Article PubMed PubMed Central Google Scholar
Rouillard AD, Gundersen GW, Fernandez NF, Wang Z, Monteiro CD, McDermott MG, Ma’ayan A (2016) The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Database (Oxford) 2016:1–16. https://doi.org/10.1093/database/baw100
CAS Article Google Scholar
Searle BO, Dasari S, Turner M, Reddy AP, Choi D, Wilmarth PA, McCormack AL, David LL, Nagalla SB (2004) High-throughput identification of proteins and unanticipated sequence modifications using a mass-based alignment algorithm for MS/MS de Novo sequencing results. Anal Chem 76:2220–2230. https://doi.org/10.1021/ac035258x
CAS Article PubMed Google Scholar
Slavotinek AM (2016) The family of crumbs genes and human disease. Mol Syndromol 7:274–281. https://doi.org/10.1159/000448109
CAS Article PubMed PubMed Central Google Scholar
Solár P, Sačková V, Hrčková G, Demečková V, Kassayová M, Bojková B, Mudroňová D, Gancarčíková S, Jendželovský R, Fedoročko P (2017) Antitumor effect of the combination of manumycin A and Immodin is associated with antiplatelet activity and increased granulocyte tumor infiltration in a 4T1 breast tumor model. Oncol Rep 37:368–378. https://doi.org/10.3892/or.2016.5265
Article PubMed Google Scholar
Sosne G, Qiu P, Kurpakus-Wheater M (2007) Thymosin beta 4: A novel corneal wound healing and anti-inflammatory agent. Clin Ophthalmol 1:201–207
CAS PubMed PubMed Central Google Scholar
Sweet DT, Chen Z, Wiley DM, Bautch VL, Tzima E (2012) The adaptor protein Shc integrates growth factor and ECM signaling during postnatal angiogenesis. Blood 119:1946–1955. https://doi.org/10.1182/blood-2011-10-384560
CAS Article PubMed PubMed Central Google Scholar
Tan W, Zhu K, Segal DJ, Barbas CF, Chow SA (2004) Fusion proteins consisting of human immunodeficiency virus type 1 integrase and the designed polydactyl zinc finger protein E2C direct integration of viral DNA into specific sites. J Virol 78:1301–1313. https://doi.org/10.1128/jvi.78.3.1301-1313.2004
CAS Article PubMed PubMed Central Google Scholar
Tayyab S, Qasim MA (1988) Biochemistry and roles of glycophorin A. Biochem Educ 16:63–66. https://doi.org/10.1016/0307-4412(88)90052-0
CAS Article Google Scholar
Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH (2014) Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 370:901–910. https://doi.org/10.1056/NEJMoa1300662
CAS Article PubMed PubMed Central Google Scholar
Thomas-Vaslin V, Six A, Pham H-P, Dansokho C, Chaara W, Gouritin B, Bellier B, Klatzm D (2012) Immunodepression and Immunosuppression During Aging. In: Kapur S, Barbosa Portela M (eds) Immunosuppression - Role in Health and Diseases. InTech, pp 125–146
Totaro A, Grifa A, Carella M, Rommens JM, Valentino MA, Roetto A, Zelante L, Gasparini P (1998) Cloning of a new gene (FB19) within HLA class I region. Biochem Biophys Res Commun 250:555–557. https://doi.org/10.1006/bbrc.1998.9354
CAS Article PubMed Google Scholar
Tsalamandris S, Oikonomou E, Papageorgiou N, Tousoulis D (2017) The role of inflammation. In: Tousoulis D (ed) Coronary Artery Disease: From Biology to Clinical Practice. Academic Press Inc., London, san Diego, Cambridge, Oxford, pp 67–94. https://doi.org/10.1016/B978-0-12-811908-2.00005-2
Vacek A, Barnet K, Hofer M, Cech KK, Pekarek J, Schneiderova H (1997) Stimulation of hemopoietic colony formation from mouse marrow cells in vitro using human dialyzable leukocyte extracts-immodin-sevac. Int J Immunopharmacol 19:431–436. https://doi.org/10.1016/S0192-0561(97)00100-8
CAS Article PubMed Google Scholar
Vacek A, Hofer M, Barnet K, Cech K, Pekárek J, Schneiderová H (2000) Positive effects of dialyzable leukocyte extract (DLE) on recovery of mouse haemopoiesis suppressed by ionizing radiation and on proliferation of haemopoietic progenitor cells in vitro. Int J Immunopharmacol 22:623–634. https://doi.org/10.1016/S0192-0561(00)00025-4
CAS Article PubMed Google Scholar
Vardabasso C, Hasson D, Ratnakumar K, Chung C-Y, Duarte LF, Bernstein E (2014) Histone variants: emerging players in cancer biology. Cell Mol Life Sci 71:379–404. https://doi.org/10.1007/s00018-013-1343-z
CAS Article PubMed Google Scholar
Wang HT, Kong JP, Ding F, Wang XQ, Wang MR, Liu LX, Wu M, Liu ZH (2003) Analysis of gene expression profile induced by EMP-1 in esophageal cancer cells using cDNA microarray. World J Gastroenterol 9:392–398. https://doi.org/10.3748/wjg.v9.i3.392
CAS Article PubMed PubMed Central Google Scholar
Wende H, Volz A, Ziegler A (2000) Extensive gene duplications and a large inversion characterize the human leukocyte receptor cluster. Immunogenetics 51:703–713. https://doi.org/10.1007/s002510000187
CAS Article PubMed Google Scholar
Wilson GB, Metcalf JF, Fudenberg HH (1982) Treatment of Mycobacterium fortuitum pulmonary infection with “transfer factor” (TF): New methodology for evaluating TF potency and predicting clinical response. Clin Immunol Immunopathol 23:478–491. https://doi.org/10.1016/0090-1229(82)90132-5
CAS Article PubMed Google Scholar
Witherden DA, Watanabe M, Garijo O, Rieder SE, Sarkisyan G, Cronin SJF, Verdino P, Wilson IA, Kumanogoh A, Kikutani H, Teyton L, Fischer WH, Havran WL (2012) The CD100 receptor interacts with Its plexin B2 ligand to regulate epidermal γδ T cell function. Immunity 37:314–325. https://doi.org/10.1016/j.immuni.2012.05.026
CAS Article PubMed PubMed Central Google Scholar
Wong MKS (2016) Kallikrein-Kinin System. In: Takei Y, Ando H, Tsutsui K (eds), Handbook of hormones-comparative endocrinology for basic and clinical research. Academic Press, Tokyo, pp. 266–267. https://doi.org/10.1016/B978-0-12-801028-0.00030-1
Yang Q, Bai S-Y, Li L-F, Li S, Zhang Y, Munir M, Qiu H-J (2019) Human hemoglobin subunit beta functions as a pleiotropic regulator of RIG-I/MDA5-mediated antiviral innate immune responses. J Virol 93:e00718-e719. https://doi.org/10.1128/jvi.00718-19
CAS Article PubMed PubMed Central Google Scholar
Yates JR, Eng JK, McCormack AL, Schieltz D (1995) Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database. Anal Chem 67:1426–1436. https://doi.org/10.1021/ac00104a020
CAS Article PubMed Google Scholar

Download references

Acknowledgements

This study was supported by a grant from the Slovak Research and Development Agency No. APVV-15-0720.

Author information

Fernando Zuniga Navarrete and Sofia G. Zavala Meneses contributed equally.

Authors and Affiliations

Institute of Virology, Biomedical Research Center of the SAS, Bratislava, Slovak Republic
Fernando Zuniga-Navarrete, Vladimir Zelnik, Juraj Kopacek & Ludovit Skultety
Institute of Microbiology of the CAS, v.v.i., Prague, Czech Republic
Sofia Guadalupe Zavala-Meneses & Ludovit Skultety

Authors

Fernando Zuniga-Navarrete
View author publications
You can also search for this author in PubMed Google Scholar
Sofia Guadalupe Zavala-Meneses
View author publications
You can also search for this author in PubMed Google Scholar
Vladimir Zelnik
View author publications
You can also search for this author in PubMed Google Scholar
Juraj Kopacek
View author publications
You can also search for this author in PubMed Google Scholar
Ludovit Skultety
View author publications
You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ludovit Skultety.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 167 KB)

Supplementary file2 (PDF 245 KB)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zuniga-Navarrete, F., Zavala-Meneses, S.G., Zelnik, V. et al. Initial proteomic characterization of IMMODIN, commercially available dialysable leukocytes extract. Chem. Pap. 75, 1959–1968 (2021). https://doi.org/10.1007/s11696-020-01467-w

Download citation

Received: 26 October 2020
Accepted: 08 December 2020
Published: 05 January 2021
Issue Date: May 2021
DOI: https://doi.org/10.1007/s11696-020-01467-w

Keywords

Dialysable leukocyte extract
Transfer factor
Immunomodulator
Protein identification
Functional prediction