ArticleMediators of inflammation2002
Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14) from target cells in its apoptosis-inducing activity.
Article in Mediators of inflammation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 66 citations in OpenAlex.
- A Serological Neoepitope Biomarker of Neutrophil Elastase-Degraded Calprotectin, Associated with Neutrophil Activity, Identifies Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease More Effectively Than Total Calprotectin.Journal of clinical medicine · 2023Article
- Regulation of zinc-dependent enzymes by metal carrier proteins.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Review
- Downregulation of S100 Calcium Binding Protein A9 in Esophageal Squamous Cell Carcinoma.TheScientificWorldJournal · 2015Article
- In solution cation-induced secondary and tertiary structure alterations of human calprotectin.The protein journal · 2014Article
- S100A8 and S100A9 Positive Cells in Colorectal Carcinoma: Clinicopathological Analysis.Gastroenterology research and practice · 2014Article
- The pro-apoptotic and pro-inflammatory effects of calprotectin on human periodontal ligament cells.PloS one · 2014Article
- Article
- Functions of S100 proteins.Current molecular medicine · 2013Review
- Cytotoxicity of superoxide dismutase 1 in cultured cells is linked to Zn2+ chelation.PloS one · 2012Article
- Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2011Article
- S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3.Cell research · 2010Article
- Microarray analysis of irradiated growth plate zones following laser microdissection shows later importance of differentially expressed genes during radiorecovery.Cells, tissues, organs · 2010Article
- ANTI-INFECTIVE PROTECTIVE PROPERTIES OF S100 CALGRANULINS.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2009Article
- S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway.Journal of leukocyte biology · 2008Article
- Zinc is a novel intracellular second messenger.The Journal of cell biology · 2007Article
- The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis.Arthritis research & therapy · 2006Article
- Regulation of S100A8/A9 (calprotectin) binding to tumor cells by zinc ion and its implication for apoptosis-inducing activity.Mediators of inflammation · 2005Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCalprotectin is a calcium-binding and zinc-binding protein complex that is abundant in the cytosol of neutrophils. This factor is composed of 8 and 14 kDa subunits, which have also been termed migration inhibitory factor-related proteins MRP8 and MRP14. We previously reported that rat calprotectin purified from inflammatory neutrophils induces apoptosis of various tumor cells or normal fibroblasts in a zinc-reversible manner.
aimThe present study was undertaken to elucidate which subunit is responsible for the apoptosis-inducing activity, and to explore the mechanism of zinc-reversible apoptosis induction.
methodsThe apoptosis-inducing activity of recombinant human MRP8 (rhMRP8) and recombinant human MRP14 (rhMRP14) was examined against EL-4 lymphoma cells in vitro. To determine whether zinc deprivation by calprotectin was essential for the cytotoxicity, the activity of calprotectin was tested under conditions where physical contact between the factor and the cells was precluded by a low molecular weight cut-off dialysis membrane.
resultsThe cytotoxicity of rhMRP14 against EL-4 cells was first detected at 10 microM in a standard medium, whereas rhMRP8 caused only marginal cytotoxicity at 40 microM. A mixture of both proteins showed higher specific activity (onset of cytotoxicity at 5 microM). When the cells were cultured in divalent cation-depleted medium, each dose-response curve was shifted to about a four-fold lower concentration range. Calprotectin was found to induce cell death even when the complex and the target cells were separated by dialysis membrane. A membrane-impermeable zinc chelator, diethylenetriamine pentaacetic acid (DTPA), also induced target cell apoptosis in a similar time-course as calprotectin. Moreover, the activities of calprotectin and DTPA were completely inhibited by the presence of zinc ions.
conclusionThese data indicate that calprotectin has higher specific activity to induce apoptosis than the Individual subunits, and that the mechanism is exclusion of zinc from target cells.
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