{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:35:24Z","timestamp":1783427724214,"version":"3.54.6"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gilead Sciences, Inc."},{"name":"Impact Communication Partners, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Matrix metalloproteinase 9 (MMP9), a protease implicated in multiple diseases, is secreted as an inactive zymogen and requires proteolytic removal of the pro-domain for activation. The relative levels and functionality of the pro- and active-MMP9 isoforms in tissues are not characterized. We generated a specific antibody that distinguishes an active form of MMP9, F107-MMP9, from the inactive pro-MMP9 isoform. Using multiple in vitro assays and specimen types, we show that F107-MMP9 expression is localized and disease-specific compared with its more abundant parental pro-form. It is detected around sites of active tissue remodeling, including fistulae of inflammatory bowel and dermal fissures in hidradenitis suppurativa, and is expressed by myeloid cells, including macrophages and neutrophils. Together, our findings provide insights into the distribution and potential role of MMP9 in inflammatory diseases.<\/jats:p>","DOI":"10.3390\/antib12010009","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T05:50:20Z","timestamp":1674107420000},"page":"9","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Characterization of Active MMP9 in Chronic Inflammatory Diseases Using a Novel Anti-MMP9 Antibody"],"prefix":"10.3390","volume":"12","author":[{"given":"Maile","family":"Velasquez","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA 94404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA 94404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Brockett","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA 94404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Mikels-Vigdal","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA 94404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Mikaelian","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA 94404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Smith","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA 94404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1470-1970","authenticated-orcid":false,"given":"Andrew E.","family":"Greenstein","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA 94404, USA"},{"name":"Corcept Therapeutics, 149 Commonwealth Dr, Menlo Park, CA 94025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25854","DOI":"10.1074\/jbc.M109.033472","article-title":"Neutrophil MMP-9 Proenzyme, Unencumbered by TIMP-1, Undergoes Efficient Activation in Vivo and Catalytically Induces Angiogenesis via a Basic Fibroblast Growth Factor (FGF-2)\/FGFR-2 Pathway","volume":"284","author":"Ardi","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.bbamcr.2009.09.017","article-title":"Pleiotropic Roles of Matrix Metalloproteinases in Tumor Angiogenesis: Contrasting, Overlapping and Compensatory Functions","volume":"1803","author":"Deryugina","year":"2010","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cell.2010.03.015","article-title":"Matrix Metalloproteinases: Regulators of the Tumor Microenvironment","volume":"141","author":"Kessenbrock","year":"2010","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12029-009-9091-x","article-title":"Prognostic Significance of Matrix Metalloproteinase-9 (MMP-9) in Stage II Colorectal Carcinoma","volume":"40","author":"Buhmeida","year":"2009","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1002\/ijc.25734","article-title":"Matrix Metalloproteinase-9 Is Associated with Disease-Free Survival and Overall Survival in Patients with Gastric Cancer","volume":"129","author":"Chu","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1245\/s10434-011-1686-3","article-title":"Matrix Metalloproteinase-9 Is Associated with Relapse and Prognosis of Patients with Colorectal Cancer","volume":"19","author":"Chu","year":"2011","journal-title":"Ann. Surg. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1093\/annonc\/mdr552","article-title":"The Validation of Matrix Metalloproteinase-9 mRNA Gene Expression as a Predictor of Outcome in Patients with Metastatic Gastric Cancer","volume":"23","author":"Pauligk","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_8","first-page":"217","article-title":"Biological and Clinical Significance of MMP-2, MMP-9, TIMP-1 and TIMP-2 in Non-Small Cell Lung Cancer","volume":"17","author":"Iniesta","year":"2007","journal-title":"Oncol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00280-005-0081-9","article-title":"The MMP-9 Expression Determined the Efficacy of Postoperative Adjuvant Chemotherapy Using Oral Fluoropyrimidines in Stage II or III Colorectal Cancer","volume":"57","author":"Ogata","year":"2005","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5287","DOI":"10.1200\/JCO.2009.23.5556","article-title":"Matrix Metalloproteinases As Novel Biomarkers and Potential Therapeutic Targets in Human Cancer","volume":"27","author":"Roy","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1002\/jso.22001","article-title":"Prognostic Impact of MMP-2 and MMP-9 Expression in Pathologic Stage IA Non-Small Cell Lung Cancer","volume":"104","author":"Shao","year":"2011","journal-title":"J. Surg. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1620\/tjem.223.67","article-title":"Matrix Metalloproteinase-9 Is a Prognostic Marker to Predict Survival of Patients Who Underwent Surgery Due to Rectal Carcinoma","volume":"223","author":"Svagzdys","year":"2011","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1073\/pnas.87.1.364","article-title":"Multiple Modes of Activation of Latent Human Fibroblast Collagenase: Evidence for the Role of a Cys73 Active-Site Zinc Complex in Latency and a \u201cCysteine Switch\u201d Mechanism for Activation","volume":"87","author":"Springman","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0006-291X(03)01405-0","article-title":"Pro-MMP-9 Activation by the MT1-MMP\/MMP-2 Axis and MMP-3: Role of TIMP-2 and Plasma Membranes","volume":"308","author":"Toth","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nmeth.2371","article-title":"Zymography Methods for Visualizing Hydrolytic Enzymes","volume":"10","author":"Vandooren","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/978-1-61779-452-0_15","article-title":"Use of Gel Zymography to Examine Matrix Metalloproteinase (Gelatinase) Expression in Brain Tissue or in Primary Glial Cultures","volume":"814","author":"Frankowski","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/B978-0-12-800141-7.00007-3","article-title":"Matrix Metalloproteinases in Biologic Samples","volume":"65","author":"Jones","year":"2014","journal-title":"Adv. Clin. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/11703","article-title":"Tumor Targeting With a Selective Gelatinase Inhibitor","volume":"17","author":"Koivunen","year":"1999","journal-title":"Nat. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1158\/0008-5472.CAN-04-3570","article-title":"Antimetastatic Activity of a Novel Mechanism-Based Gelatinase Inhibitor","volume":"65","author":"Arlt","year":"2005","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"37585","DOI":"10.1074\/jbc.M611500200","article-title":"A Biochemical Model of Matrix Metalloproteinase 9 Activation and Inhibition","volume":"282","author":"Vempati","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8289","DOI":"10.1021\/bi012076t","article-title":"Engineering Autoactivating Forms of Matrix Metalloproteinase-9 and Expression of the Active Enzyme in Cultured Cells and Transgenic Mouse Brain","volume":"41","author":"Fisher","year":"2002","journal-title":"Biochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13066","DOI":"10.1074\/jbc.274.19.13066","article-title":"Activation of Matrix Metalloproteinase-9 (MMP-9) via a Converging Plasmin\/Stromelysin-1 Cascade Enhances Tumor Cell Invasion","volume":"274","author":"Sipley","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.bbamcr.2009.09.016","article-title":"Avoiding Spam in the Proteolytic Internet: Future Strategies for Anti-Metastatic MMP Inhibition","volume":"1803","author":"Kates","year":"2010","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/nrd4390","article-title":"Is There New Hope for Therapeutic Matrix Metalloproteinase Inhibition?","volume":"13","author":"Vandenbroucke","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/978-1-4939-7111-4_8","article-title":"Zymography as a Research Tool in the Study of Matrix Metalloproteinase Inhibitors","volume":"1626","author":"Ren","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Marshall, D.C., Lyman, S.K., McCauley, S., Kovalenko, M., Spangler, R., Liu, C., Lee, M., O\u2019Sullivan, C., Barry-Hamilton, V., and Ghermazien, H. (2015). Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127063"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6810","DOI":"10.1074\/jbc.M116.760579","article-title":"Biochemical Characterization and Structure Determination of a Potent, Selective Antibody Inhibitor of Human MMP9","volume":"292","author":"Appleby","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.clinthera.2017.11.011","article-title":"Phase 1b Study of the Safety, Pharmacokinetics, and Disease-related Outcomes of the Matrix Metalloproteinase-9 Inhibitor Andecaliximab in Patients With Rheumatoid Arthritis","volume":"40","author":"Gossage","year":"2018","journal-title":"Clin. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/apt.13653","article-title":"Randomised Clinical Trial: A Phase 1, Dose-Ranging Study of the Anti-Matrix Metalloproteinase-9 Monoclonal Antibody GS-5745 Versus Placebo for Ulcerative Colitis","volume":"44","author":"Sandborn","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0925-4439(01)00080-1","article-title":"The Inhibitory Effects of Immunosuppressive Factors, Dexamethasone and Interleukin-4, on NF-KappaB-Mediated Protease Production by Oral Cancer","volume":"1586","author":"Beppu","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.1016\/S0021-9258(19)50563-4","article-title":"Matrix Metalloproteinase 3 (Stromelysin) Activates the Precursor for the Human Matrix Metalloproteinase 9","volume":"267","author":"Ogata","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6691","DOI":"10.1074\/jbc.270.12.6691","article-title":"Matrix Metalloproteinase 7 (Matrilysin) From Human Rectal Carcinoma Cells. Activation of the Precursor, Interaction With Other Matrix Metalloproteinases and Enzymic Properties","volume":"270","author":"Imai","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pittayapruek, P., Meephansan, J., Prapapan, O., Komine, M., and Ohtsuki, M. (2016). Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060868"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100305","DOI":"10.1101\/pdb.prot100305","article-title":"Standard Immunization of Rabbits","volume":"2020","author":"Greenfield","year":"2020","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1002\/jcb.21675","article-title":"MMP-14 Mediated MMP-9 Expression is Involved in TGF-Beta1-Induced Keratinocyte Migration","volume":"104","author":"Seomun","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0163-7258(97)00023-5","article-title":"Matrix Metalloproteinase Inhibition as a Novel Anticancer Strategy: A Review with Special Focus on Batimastat and Marimastat","volume":"75","author":"Rasmussen","year":"1997","journal-title":"Pharmacol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.bpobgyn.2014.07.012","article-title":"Hidradenitis Suppurativa","volume":"28","author":"Margesson","year":"2014","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1074\/mcp.M800095-MCP200","article-title":"Novel MMP-9 Substrates in Cancer Cells Revealed by a Label-free Quantitative Proteomics Approach","volume":"7","author":"Xu","year":"2008","journal-title":"Mol. Cell. Proteom."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.bbrc.2003.09.098","article-title":"Carboxyterminal Cleavage of the Chemokines MIG and IP-10 by Gelatinase B and Neutrophil Collagenase","volume":"310","author":"Husson","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1128\/CDLI.10.2.308-314.2003","article-title":"Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease","volume":"10","author":"Chua","year":"2003","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.nmd.2011.05.011","article-title":"Serum Matrix Metalloproteinase-9 (MMP-9) as a Biomarker for Monitoring Disease Progression in Duchenne Muscular Dystrophy (DMD)","volume":"21","author":"Nadarajah","year":"2011","journal-title":"Neuromuscul. Disord."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7060","DOI":"10.4049\/jimmunol.172.11.7060","article-title":"Intracellular and Cell Surface Localization of a Complex Between AlphaMbeta2 Integrin and Promatrix Metalloproteinase-9 Progelatinase in Neutrophils","volume":"172","author":"Stefanidakis","year":"2004","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Christensen, J., and Shastri, V.P. (2015). Matrix-Metalloproteinase-9 is Cleaved and Activated by Cathepsin K. BMC Res. Notes, 8.","DOI":"10.1186\/s13104-015-1284-8"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jneuroim.2004.09.015","article-title":"The Pro and the Active Form of Matrix Metalloproteinase-9 is Increased in Serum of Patients With Amyotrophic Lateral Sclerosis","volume":"159","author":"Demestre","year":"2005","journal-title":"J. Neuroimmunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1016\/j.bbrc.2017.10.009","article-title":"MMP-9-Cleaved Osteopontin Isoform Mediates Tumor Immune Escape by Inducing Expansion of Myeloid-Derived Suppressor Cells","volume":"493","author":"Shao","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11438","DOI":"10.1158\/0008-5472.CAN-07-1882","article-title":"Amino-Biphosphonate\u2013Mediated MMP-9 Inhibition Breaks the Tumor-Bone Marrow Axis Responsible for Myeloid-Derived Suppressor Cell Expansion and Macrophage Infiltration in Tumor Stroma","volume":"67","author":"Melani","year":"2007","journal-title":"Cancer Res"}],"container-title":["Antibodies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4468\/12\/1\/9\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:09:31Z","timestamp":1760119771000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4468\/12\/1\/9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["antib12010009"],"URL":"https:\/\/doi.org\/10.3390\/antib12010009","relation":{},"ISSN":["2073-4468"],"issn-type":[{"value":"2073-4468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]}}}