{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:05:20Z","timestamp":1784887520015,"version":"3.55.0"},"reference-count":80,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Doktor Robert Pfleger Stiftung Bamberg","award":["RDR\/chu"],"award-info":[{"award-number":["RDR\/chu"]}]},{"name":"Foundation for Pathobiochemistry and Molecular Diagnostics (SPMD) of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL)","award":["RDR\/chu"],"award-info":[{"award-number":["RDR\/chu"]}]},{"name":"Hannover Biomedical Research School (HBRS)","award":["RDR\/chu"],"award-info":[{"award-number":["RDR\/chu"]}]},{"name":"MD\/PhD program Molecular Medicine","award":["RDR\/chu"],"award-info":[{"award-number":["RDR\/chu"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In contrast to other common anticoagulants such as citrate and low-molecular-weight heparin (LMWH), high-molecular-weight heparin (HMWH) induces the expression of matrix metalloproteinase (MMP)-9, which is also measured as a biomarker for stroke in blood samples. Mechanistically, HMWH-stimulated T cells produce cytokines that induce monocytic MMP-9 expression. Here, the influence of further anticoagulants (Fondaparinux, Hirudin, and Alteplase) and the heparin-contaminating glycosaminoglycans (GAG) hyaluronic acid (HA), dermatan sulfate (DS), chondroitin sulfate (CS), and over-sulfated CS (OSCS) on MMP-9 was analyzed to assess its suitability as a biomarker under various conditions. Therefore, starved Jurkat T cells were stimulated with anticoagulants\/contaminants. Subsequently, starved monocytic THP-1 cells were incubated with the conditioned Jurkat supernatant, and MMP-9 mRNA levels were monitored (quantitative (q)PCR). Jurkat-derived mediators secreted in response to anticoagulants\/contaminants were also assessed (proteome profiler array). The supernatants of HMWH-, Hirudin-, CS-, and OSCS-treated Jurkat cells comprised combinations of activating mediators and led to a significant (in the case of OSCS, dramatic) MMP-9 induction in THP-1. HA induced MMP-9 only in high concentrations, while LMWH, Fondaparinux, Alteplase, and DS had no effect. This indicates that depending on molecular weight and charge (but independent of anticoagulant activity), anticoagulants\/contaminants provoke the expression of T-cell-derived cytokines\/chemokines that induce monocytic MMP-9 expression, thus potentially impairing the diagnostic validity of MMP-9.<\/jats:p>","DOI":"10.3390\/ijms251810106","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T04:31:23Z","timestamp":1726806683000},"page":"10106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Influence of Anticoagulants and Heparin Contaminants on the Suitability of MMP-9 as a Blood-Derived Biomarker"],"prefix":"10.3390","volume":"25","author":[{"given":"Daniela","family":"K\u00fcper","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefin","family":"Klos","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"K\u00fchl","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4555-3074","authenticated-orcid":false,"given":"Rozan","family":"Attili","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Faculty of Pharmacy and Medical Sciences, Hebron University, Hebron 711, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korbinian","family":"Brand","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Weissenborn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Lichtinghagen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-9935","authenticated-orcid":false,"given":"Ren\u00e9","family":"Huber","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.2741\/4462","article-title":"Heparin and anticoagulation","volume":"21","author":"Onishi","year":"2016","journal-title":"Front. Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mendes, A., Meneghetti, M.C.Z., Palladino, M.V., Justo, G.Z., Sassaki, G.L., Fareed, J., Lima, M.A., and Nader, H.B. (2019). Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants. Molecules, 24.","DOI":"10.3390\/molecules24162988"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Oduah, E.I., Linhardt, R.J., and Sharfstein, S.T. (2016). Heparin: Past, Present, and Future. Pharmaceuticals, 9.","DOI":"10.3390\/ph9030038"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1177\/0091270009355158","article-title":"Structure elucidation and biological activity of the oversulfated chondroitin sulfate contaminant in Baxter heparin","volume":"50","author":"McKee","year":"2010","journal-title":"J. Clin. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1182\/blood-2016-11-709873","article-title":"Heparin-induced thrombocytopenia","volume":"129","author":"Arepally","year":"2017","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cca.2022.10.006","article-title":"Evaluation of a novel heparin-iloprost-based antithrombotic formulation blood collection tube for clinical usage","volume":"537","author":"Wiwe","year":"2022","journal-title":"Clin. Chim. Acta"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1160\/TH08-01-0032","article-title":"Heparin and low-molecular-weight heparin","volume":"99","author":"Gray","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hogwood, J., Gray, E., and Mulloy, B. (2023). Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020271"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1039\/b819896a","article-title":"Lessons learned from the contamination of heparin","volume":"26","author":"Liu","year":"2009","journal-title":"Nat. Prod. Rep."},{"key":"ref_10","unstructured":"(2020). European Pharmacopoeia, Deutscher Apotheker Verlag. [10th ed.]."},{"key":"ref_11","unstructured":"(2021). United States Pharmacopeia, USP 44\u2014NF 39, United States Pharmacopeia."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nbt1407","article-title":"Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events","volume":"26","author":"Guerrini","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/j.1398-9995.1994.tb01131.x","article-title":"Contamination of heparin by histamine: Measurement and characterization by high-performance liquid chromatography and radioimmunoassay","volume":"49","author":"Hermann","year":"1994","journal-title":"Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/S0140-6736(87)90510-1","article-title":"Bleeding associated with heparin contaminants","volume":"1","author":"Casu","year":"1987","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nbt0310-203","article-title":"Oversulfated chondroitin sulfate is not the sole contaminant in heparin","volume":"28","author":"Pan","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ejps.2010.04.002","article-title":"Composition of OSCS-contaminated heparin occurring in 2008 in batches on the German market","volume":"40","author":"Beyer","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.bbadis.2014.04.031","article-title":"Correlation between MMP-9 and extracellular cytokine HMGB1 in prediction of human ischemic stroke outcome","volume":"1842","author":"Sapojnikova","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Huang, H. (2018). Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances. Sensors, 18.","DOI":"10.3390\/s18103249"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.clinbiochem.2012.01.028","article-title":"Anticoagulants affect matrix metalloproteinase 9 levels in blood samples of stroke patients and healthy controls","volume":"45","author":"Rababah","year":"2012","journal-title":"Clin. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Huber, R., Attili\/Abedalkhader, R., Kuper, D., Hauke, L., Luns, B., Brand, K., Weissenborn, K., and Lichtinghagen, R. (2019). Cellular and Molecular Effects of High-Molecular-Weight Heparin on Matrix Metalloproteinase 9 Expression. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071595"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.clinbiochem.2006.10.007","article-title":"Rapid separation of serum does not avoid artificially higher matrix metalloproteinase (MMP)-9 levels in serum versus plasma","volume":"40","author":"Gerlach","year":"2007","journal-title":"Clin. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.clinbiochem.2008.09.104","article-title":"Heparin affects matrix metalloproteinases and tissue inhibitors of metalloproteinases circulating in peripheral blood","volume":"41","author":"Mannello","year":"2008","journal-title":"Clin. Biochem."},{"key":"ref_23","first-page":"129","article-title":"Treatment of proximal deep-vein thrombosis using subcutaneously administered calcium heparin: Comparison with intravenous sodium heparin","volume":"22","author":"White","year":"1992","journal-title":"Haemostasis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1517\/13543784.11.3.397","article-title":"Fondaparinux: A synthetic heparin pentasaccharide as a new antithrombotic agent","volume":"11","author":"Walenga","year":"2002","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nrd2308","article-title":"Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases","volume":"6","author":"Hu","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wollbold, J., Huber, R., Pohlers, D., Koczan, D., Guthke, R., Kinne, R.W., and Gausmann, U. (2009). Adapted Boolean network models for extracellular matrix formation. BMC Syst. Biol., 3.","DOI":"10.1186\/1752-0509-3-77"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/bs.apha.2017.08.002","article-title":"Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease","volume":"81","author":"Wang","year":"2018","journal-title":"Adv. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41569-018-0022-z","article-title":"Assigning matrix metalloproteinase roles in ischaemic cardiac remodelling","volume":"15","author":"Lindsey","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.1093\/brain\/awg285","article-title":"Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis","volume":"126","author":"Nuttall","year":"2003","journal-title":"Brain"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Olejarz, W., Lacheta, D., and Kubiak-Tomaszewska, G. (2020). Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113946"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nikolov, A., and Popovski, N. (2021). Role of Gelatinases MMP-2 and MMP-9 in Healthy and Complicated Pregnancy and Their Future Potential as Preeclampsia Biomarkers. Diagnostics, 11.","DOI":"10.3390\/diagnostics11030480"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1039\/C4NP00076E","article-title":"Chemoenzymatic synthesis of heparan sulfate and heparin","volume":"31","author":"Liu","year":"2014","journal-title":"Nat. Prod. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/MCP.0b013e328216430d","article-title":"Low molecular weight heparin and bleeding in patients with chronic renal failure","volume":"13","author":"Crowther","year":"2007","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.cca.2009.01.026","article-title":"Preanalytical variables in measurement of free (ionized) calcium in lithium heparin-containing blood collection tubes","volume":"403","author":"Haverstick","year":"2009","journal-title":"Clin. Chim. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.clinbiochem.2022.04.017","article-title":"Comparison of blood collection tubes for 29 biochemical analytes in pediatric patients with central venous catheters","volume":"107","author":"Kang","year":"2022","journal-title":"Clin. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"705","DOI":"10.7754\/Clin.Lab.2015.150839","article-title":"The Influence of Blood Collection Tubes on Measurement of Cardiac Biomarkers","volume":"62","author":"Lan","year":"2016","journal-title":"Clin. Lab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"371","DOI":"10.5435\/00124635-200411000-00001","article-title":"Fondaparinux","volume":"12","author":"Turpie","year":"2004","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/bs.pmbts.2019.02.004","article-title":"The clinical use of Fondaparinux: A synthetic heparin pentasaccharide","volume":"163","author":"Zhang","year":"2019","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/imj.13659","article-title":"Non-immediate heparin and heparinoid cutaneous allergic reactions: A role for fondaparinux","volume":"48","author":"Tan","year":"2018","journal-title":"Intern. Med. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bundhun, P.K., Shaik, M., and Yuan, J. (2017). Choosing between Enoxaparin and Fondaparinux for the management of patients with acute coronary syndrome: A systematic review and meta-analysis. BMC Cardiovasc. Disord., 17.","DOI":"10.1186\/s12872-017-0552-z"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1055\/s-2002-35293","article-title":"Pharmacology of recombinant hirudin","volume":"28","author":"Nowak","year":"2002","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Junren, C., Xiaofang, X., Huiqiong, Z., Gangmin, L., Yanpeng, Y., Xiaoyu, C., Yuqing, G., Yanan, L., Yue, Z., and Fu, P. (2021). Pharmacological Activities and Mechanisms of Hirudin and Its Derivatives\u2014A Review. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.660757"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1515\/CCLM.2001.204","article-title":"The use of hirudin as universal anticoagulant in haematology, clinical chemistry and blood grouping","volume":"39","author":"Menssen","year":"2001","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/10408363.2020.1849008","article-title":"Clot activators and anticoagulant additives for blood collection. A critical review on behalf of COLABIOCLI WG-PRE-LATAM","volume":"58","author":"Varela","year":"2021","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1161\/ATVBAHA.108.179655","article-title":"The tissue-type plasminogen activator story","volume":"29","author":"Collen","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1161\/STR.0000000000000086","article-title":"Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association\/American Stroke Association","volume":"47","author":"Demaerschalk","year":"2016","journal-title":"Stroke"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1177\/1060028015579988","article-title":"Low-Dose Systemic Alteplase (tPA) for the Treatment of Pulmonary Embolism","volume":"49","author":"Brandt","year":"2015","journal-title":"Ann. Pharmacother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"899","DOI":"10.2165\/11209940-000000000-00000","article-title":"Alteplase: A review of its use in the management of acute ischaemic stroke","volume":"26","author":"Dhillon","year":"2012","journal-title":"CNS Drugs"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nbt.3606","article-title":"The US regulatory and pharmacopeia response to the global heparin contamination crisis","volume":"34","author":"Szajek","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Marinho, A., Nunes, C., and Reis, S. (2021). Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation. Biomolecules, 11.","DOI":"10.3390\/biom11101518"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Fallacara, A., Baldini, E., Manfredini, S., and Vertuani, S. (2018). Hyaluronic Acid in the Third Millennium. Polymers, 10.","DOI":"10.3390\/polym10070701"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.3390\/molecules20034277","article-title":"Discrepancies in composition and biological effects of different formulations of chondroitin sulfate","volume":"20","author":"Farran","year":"2015","journal-title":"Molecules"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1160\/TH09-10-0734","article-title":"Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides","volume":"103","author":"Fonseca","year":"2010","journal-title":"Thromb. Haemost."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wang, W., Shi, L., Qin, Y., and Li, F. (2020). Research and Application of Chondroitin Sulfate\/Dermatan Sulfate-Degrading Enzymes. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.560442"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"27597","DOI":"10.1074\/jbc.274.39.27597","article-title":"Comparison of heparin- and dermatan sulfate-mediated catalysis of thrombin inactivation by heparin cofactor II","volume":"274","author":"Liaw","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Volpi, N. (2019). Chondroitin Sulfate Safety and Quality. Molecules, 24.","DOI":"10.3390\/molecules24081447"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1369\/0022155412459857","article-title":"Iduronic acid in chondroitin\/dermatan sulfate: Biosynthesis and biological function","volume":"60","author":"Malmstrom","year":"2012","journal-title":"J. Histochem. Cytochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1160\/TH09-01-0064","article-title":"Heparins: Process-related physico-chemical and compositional characteristics, fingerprints and impurities","volume":"102","author":"Liverani","year":"2009","journal-title":"Thromb. Haemost."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1177\/1076029611421167","article-title":"Interactions of oversulfated chondroitin sulfate (OSCS) from different sources with unfractionated heparin","volume":"18","author":"Gray","year":"2012","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"22966","DOI":"10.1074\/jbc.M109.063735","article-title":"Chemically oversulfated glycosaminoglycans are potent modulators of contact system activation and different cell signaling pathways","volume":"285","author":"Pan","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.bcp.2009.04.012","article-title":"Oversulfated chondroitin sulfate interaction with heparin-binding proteins: New insights into adverse reactions from contaminated heparins","volume":"78","author":"Li","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Hogwood, J., Naggi, A., Torri, G., Page, C., Rigsby, P., Mulloy, B., and Gray, E. (2018). The effect of increasing the sulfation level of chondroitin sulfate on anticoagulant specific activity and activation of the kinin system. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193482"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/MBC.0b013e3282f2a99e","article-title":"Effect of oversulfation on the chemical and biological properties of chondroitin-4-sulfate","volume":"19","author":"Carranza","year":"2008","journal-title":"Blood Coagul. Fibrinolysis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1055\/s-0028-1086092","article-title":"Biological Profile of the Hyper\/Oversulfated Chondroitin Sulfate Contaminant Isolated from Recalled Heparin","volume":"34","author":"Fareed","year":"2008","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s10719-016-9720-0","article-title":"Chondroitin sulfate\/dermatan sulfate sulfatases from mammals and bacteria","volume":"33","author":"Wang","year":"2016","journal-title":"Glycoconj. J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1365-2141.1992.tb08216.x","article-title":"Heparin-associated thrombocytopenia in a patient treated with polysulphated chondroitin sulphate: Evidence for immunological crossreactivity between heparin and polysulphated glycosaminoglycan","volume":"81","author":"Greinacher","year":"1992","journal-title":"Br. J. Haematol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1517\/14740330902778180","article-title":"Heparin-induced anaphylactic and anaphylactoid reactions: Two distinct but overlapping syndromes","volume":"8","author":"Warkentin","year":"2009","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1212\/WNL.53.7.1402","article-title":"Changes of serum sICAM-1 and MMP-9 induced by rIFNbeta-1b treatment in relapsing-remitting MS","volume":"53","author":"Trojano","year":"1999","journal-title":"Neurology"},{"key":"ref_69","first-page":"3694","article-title":"IL-22 promotes the migration and invasion of gastric cancer cells via IL-22R1\/AKT\/MMP-9 signaling","volume":"7","author":"Ji","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kim, E.Y., Choi, B., Kim, J.E., Park, S.O., Kim, S.M., and Chang, E.J. (2020). Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P\/SIPR Signaling. Cells, 9.","DOI":"10.3390\/cells9010131"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1165\/rcmb.2003-0285OC","article-title":"Interleukin-22: A potential immunomodulatory molecule in the lung","volume":"31","author":"Whittington","year":"2004","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1080\/10409230290771546","article-title":"Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9)","volume":"37","author":"Dubois","year":"2002","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nrd4534","article-title":"Unleashing the therapeutic potential of human kallikrein-related serine proteases","volume":"14","author":"Prassas","year":"2015","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.bbrc.2013.03.001","article-title":"Human tissue kallikreins 3 and 5 can act as plasminogen activator releasing active plasmin","volume":"433","author":"Melo","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1007\/BF02045412","article-title":"Effect of heparin on the course of experimental nephritis-nephrosis","volume":"125","author":"Sartorius","year":"1955","journal-title":"Z. Gesamte Exp. Med."},{"key":"ref_76","unstructured":"Fr\u00f6mke, J. (2006). Einsatz und Wirkung von Medikamenten. Standardoperationen in der Gef\u00e4\u00dfchirurgie, Steinkopff Verlag."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s00393-003-0472-4","article-title":"Comparison of conventional and real-time RT-PCR for the quantitation of jun protooncogene mRNA and analysis of junB mRNA expression in synovial membranes and isolated synovial fibroblasts from rheumatoid arthritis patients","volume":"62","author":"Huber","year":"2003","journal-title":"Z. Rheumatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.4049\/jimmunol.1301610","article-title":"Identification of two forms of TNF tolerance in human monocytes: Differential inhibition of NF-kappaB\/AP-1- and PP1-associated signaling","volume":"192","author":"Gunther","year":"2014","journal-title":"J. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jhep.2008.03.020","article-title":"Hepatic expression of A disintegrin and metalloproteinase (ADAM) and ADAMs with thrombospondin motives (ADAM-TS) enzymes in patients with chronic liver diseases","volume":"49","author":"Schwettmann","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"22716","DOI":"10.1074\/jbc.M110.152538","article-title":"CCAAT\/enhancer-binding protein beta inhibits proliferation in monocytic cells by affecting the retinoblastoma protein\/E2F\/cyclin E pathway but is not directly required for macrophage morphology","volume":"286","author":"Gutsch","year":"2011","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/10106\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:00:32Z","timestamp":1760112032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/10106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,20]]},"references-count":80,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms251810106"],"URL":"https:\/\/doi.org\/10.3390\/ijms251810106","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,20]]}}}