Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 18

Publication Record

Connections

The Innate Immune Protein S100A9 Protects from T-Helper Cell Type 2-mediated Allergic Airway Inflammation.
Palmer LD, Maloney KN, Boyd KL, Goleniewska AK, Toki S, Maxwell CN, Chazin WJ, Peebles RS, Newcomb DC, Skaar EP
(2019) Am J Respir Cell Mol Biol 61: 459-468
MeSH Terms: Adaptive Immunity, Allergens, Alternaria, Alveolitis, Extrinsic Allergic, Animals, Bronchial Hyperreactivity, Bronchoalveolar Lavage Fluid, Calgranulin A, Calgranulin B, Cytokines, Forkhead Transcription Factors, Immunoglobulin E, Inflammation, Leukocyte L1 Antigen Complex, Lung, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Pulmonary Eosinophilia, Specific Pathogen-Free Organisms, T-Lymphocytes, Regulatory, Th2 Cells
Show Abstract · Added April 7, 2019
Calprotectin is a heterodimer of the proteins S100A8 and S100A9, and it is an abundant innate immune protein associated with inflammation. In humans, calprotectin transcription and protein abundance are associated with asthma and disease severity. However, mechanistic studies in experimental asthma models have been inconclusive, identifying both protective and pathogenic effects of calprotectin. To clarify the role of calprotectin in asthma, calprotectin-deficient and wild-type (WT) C57BL/6 mice were compared in a murine model of allergic airway inflammation. Mice were intranasally challenged with extracts of the clinically relevant allergen, (Alt Ext), or PBS every third day over 9 days. On Day 10, BAL fluid and lung tissue homogenates were harvested and allergic airway inflammation was assessed. Alt Ext challenge induced release of S100A8/S100A9 to the alveolar space and increased protein expression in the alveolar epithelium of WT mice. Compared with WT mice, mice displayed significantly enhanced allergic airway inflammation, including production of IL-13, CCL11, CCL24, serum IgE, eosinophil recruitment, and airway resistance and elastance. In response to Alt Ext, mice accumulated significantly more IL-13IL-5CD4 T-helper type 2 cells. mice also accumulated a significantly lower proportion of CD4 T regulatory (Treg) cells in the lung that had significantly lower expression of CD25. Calprotectin enhanced WT Treg cell suppressive activity . Therefore, this study identifies a role for the innate immune protein, S100A9, in protection from CD4 T-helper type 2 cell hyperinflammation in response to Alt Ext. This protection is mediated, at least in part, by CD4 Treg cell function.
0 Communities
2 Members
0 Resources
23 MeSH Terms
Expression of Calgranulin Genes S100A8, S100A9 and S100A12 Is Modulated by n-3 PUFA during Inflammation in Adipose Tissue and Mononuclear Cells.
Shah RD, Xue C, Zhang H, Tuteja S, Li M, Reilly MP, Ferguson JF
(2017) PLoS One 12: e0169614
MeSH Terms: Adipose Tissue, Adult, Antioxidants, Buttocks, Calgranulin A, Calgranulin B, Case-Control Studies, Docosahexaenoic Acids, Eicosapentaenoic Acid, Endotoxemia, Female, Gene Expression Regulation, Healthy Volunteers, Humans, Lipopolysaccharides, Male, Monocytes, S100A12 Protein, Signal Transduction
Show Abstract · Added June 6, 2017
Calgranulin genes (S100A8, S100A9 and S100A12) play key immune response roles in inflammatory disorders, including cardiovascular disease. Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) may have systemic and adipose tissue-specific anti-inflammatory and cardio-protective action. Interactions between calgranulins and the unsaturated fatty acid arachidonic acid (AA) have been reported, yet little is known about the relationship between calgranulins and the LC n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We explored tissue-specific action of calgranulins in the setting of evoked endotoxemia and n-3 PUFA supplementation. Expression of calgranulins in adipose tissue in vivo was assessed by RNA sequencing (RNASeq) before and after n-3 PUFA supplementation and evoked endotoxemia in the fenofibrate and omega-3 fatty acid modulation of endotoxemia (FFAME) Study. Subjects received n-3 PUFA (n = 8; 3600mg/day EPA/DHA) or matched placebo (n = 6) for 6-8 weeks, before completing an endotoxin challenge (LPS 0.6 ng/kg). Calgranulin genes were up-regulated post-LPS, with greater increase in n-3 PUFA (S100A8 15-fold, p = 0.003; S100A9 7-fold, p = 0.003; S100A12 28-fold, p = 0.01) compared to placebo (S100A8 2-fold, p = 0.01; S100A9 1.4-fold, p = 0.4; S100A12 5-fold, p = 0.06). In an independent evoked endotoxemia study, calgranulin gene expression correlated with the systemic inflammatory response. Through in vivo and in vitro interrogation we highlight differential responses in adipocytes and mononuclear cells during inflammation, with n-3 PUFA leading to increased calgranulin expression in adipose, but decreased expression in circulating cells. In conclusion, we present a novel relationship between n-3 PUFA anti-inflammatory action in vivo and cell-specific modulation of calgranulin expression during innate immune activation.
0 Communities
1 Members
0 Resources
19 MeSH Terms
Zinc and Manganese Chelation by Neutrophil S100A8/A9 (Calprotectin) Limits Extracellular Aspergillus fumigatus Hyphal Growth and Corneal Infection.
Clark HL, Jhingran A, Sun Y, Vareechon C, de Jesus Carrion S, Skaar EP, Chazin WJ, Calera JA, Hohl TM, Pearlman E
(2016) J Immunol 196: 336-44
MeSH Terms: Adolescent, Adult, Aged, Animals, Aspergillus fumigatus, Biological Transport, Calgranulin A, Calgranulin B, Chelating Agents, Cornea, Disease Models, Animal, Humans, Hyphae, Keratitis, Leukocyte L1 Antigen Complex, Manganese, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Neutrophils, Phagocytosis, Pulmonary Aspergillosis, Spores, Fungal, Young Adult, Zinc
Show Abstract · Added February 5, 2016
Calprotectin, a heterodimer of S100A8 and S100A9, is an abundant neutrophil protein that possesses antimicrobial activity primarily because of its ability to chelate zinc and manganese. In the current study, we showed that neutrophils from calprotectin-deficient S100A9(-/-) mice have an impaired ability to inhibit Aspergillus fumigatus hyphal growth in vitro and in infected corneas in a murine model of fungal keratitis; however, the ability to inhibit hyphal growth was restored in S100A9(-/-) mice by injecting recombinant calprotectin. Furthermore, using recombinant calprotectin with mutations in either the Zn and Mn binding sites or the Mn binding site alone, we show that both zinc and manganese binding are necessary for calprotectin's antihyphal activity. In contrast to hyphae, we found no role for neutrophil calprotectin in uptake or killing of intracellular A. fumigatus conidia either in vitro or in a murine model of pulmonary aspergillosis. We also found that an A. fumigatus ∆zafA mutant, which demonstrates deficient zinc transport, exhibits impaired growth in infected corneas and following incubation with neutrophils or calprotectin in vitro as compared with wild-type. Collectively, these studies demonstrate a novel stage-specific susceptibility of A. fumigatus to zinc and manganese chelation by neutrophil-derived calprotectin.
Copyright © 2015 by The American Association of Immunologists, Inc.
0 Communities
2 Members
0 Resources
26 MeSH Terms
Imaging mass spectrometry for assessing temporal proteomics: analysis of calprotectin in Acinetobacter baumannii pulmonary infection.
Moore JL, Becker KW, Nicklay JJ, Boyd KL, Skaar EP, Caprioli RM
(2014) Proteomics 14: 820-828
MeSH Terms: Acinetobacter Infections, Acinetobacter baumannii, Animals, Calgranulin A, Calgranulin B, Humans, Immunity, Innate, Leukocyte L1 Antigen Complex, Lung, Mice, Molecular Imaging, Neutrophils, Proteomics, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Show Abstract · Added March 7, 2014
Imaging MS is routinely used to show spatial localization of proteins within a tissue sample and can also be employed to study temporal protein dynamics. The antimicrobial S100 protein calprotectin, a heterodimer of subunits S100A8 and S100A9, is an abundant cytosolic component of neutrophils. Using imaging MS, calprotectin can be detected as a marker of the inflammatory response to bacterial challenge. In a murine model of Acinetobacter baumannii pneumonia, protein images of S100A8 and S100A9 collected at different time points throughout infection aid in visualization of the innate immune response to this pathogen. Calprotectin is detectable within 6 h of infection as immune cells respond to the invading pathogen. As the bacterial burden decreases, signals from the inflammatory proteins decrease. Calprotectin is no longer detectable 96-144 h post infection, correlating to a lack of detectable bacterial burden in lungs. These experiments provide a label-free, multiplexed approach to study host response to a bacterial threat and eventual clearance of the pathogen over time.
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
1 Communities
3 Members
0 Resources
14 MeSH Terms
Biomolecular signatures of diabetic wound healing by structural mass spectrometry.
Hines KM, Ashfaq S, Davidson JM, Opalenik SR, Wikswo JP, McLean JA
(2013) Anal Chem 85: 3651-9
MeSH Terms: Animals, Calgranulin A, Cholic Acid, Diabetes Complications, Diabetes Mellitus, Experimental, Equipment Design, Lysophosphatidylcholines, Polyvinyl Alcohol, Rats, Rats, Sprague-Dawley, Spectrometry, Mass, Electrospray Ionization, Wound Healing
Show Abstract · Added March 7, 2014
Wound fluid is a complex biological sample containing byproducts associated with the wound repair process. Contemporary techniques, such as immunoblotting and enzyme immunoassays, require extensive sample manipulation and do not permit the simultaneous analysis of multiple classes of biomolecular species. Structural mass spectrometry, implemented as ion mobility-mass spectrometry (IM-MS), comprises two sequential, gas-phase dispersion techniques well suited for the study of complex biological samples because of its ability to separate and simultaneously analyze multiple classes of biomolecules. As a model of diabetic wound healing, poly(vinyl alcohol) sponges were inserted subcutaneously into nondiabetic (control) and streptozotocin-induced diabetic rats to elicit a granulation tissue response and to collect acute wound fluid. Sponges were harvested at days 2 or 5 to capture different stages of the early wound-healing process. Utilizing IM-MS, statistical analysis, and targeted ultraperformance liquid chromatography analysis, biomolecular signatures of diabetic wound healing have been identified. The protein S100-A8 was highly enriched in the wound fluids collected from day 2 diabetic rats. Lysophosphatidylcholine (20:4) and cholic acid also contributed significantly to the differences between diabetic and control groups. This report provides a generalized workflow for wound fluid analysis demonstrated with a diabetic rat model.
1 Communities
2 Members
0 Resources
12 MeSH Terms
Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens.
Damo SM, Kehl-Fie TE, Sugitani N, Holt ME, Rathi S, Murphy WJ, Zhang Y, Betz C, Hench L, Fritz G, Skaar EP, Chazin WJ
(2013) Proc Natl Acad Sci U S A 110: 3841-6
MeSH Terms: Amino Acid Substitution, Binding Sites, Calgranulin A, Calgranulin B, Crystallography, X-Ray, Histidine, Host-Pathogen Interactions, Humans, Immunity, Innate, Leukocyte L1 Antigen Complex, Manganese, Models, Molecular, Mutagenesis, Site-Directed, Protein Multimerization, Recombinant Proteins, Staphylococcus aureus, Zinc
Show Abstract · Added March 7, 2014
The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed "nutritional immunity." CP binds Mn(2+) and Zn(2+) with high affinity and starves bacteria of these essential nutrients. Combining biophysical, structural, and microbiological analysis, we identified the molecular basis of Mn(2+) sequestration. The asymmetry of the CP heterodimer creates a single Mn(2+)-binding site from six histidine residues, which distinguishes CP from all other Mn(2+)-binding proteins. Analysis of CP mutants with altered metal-binding properties revealed that, despite both Mn(2+) and Zn(2+) being essential metals, maximal growth inhibition of multiple bacterial pathogens requires Mn(2+) sequestration. These data establish the importance of Mn(2+) sequestration in defense against infection, explain the broad-spectrum antimicrobial activity of CP relative to other S100 proteins, and clarify the impact of metal depletion on the innate immune response to infection.
0 Communities
3 Members
0 Resources
17 MeSH Terms
S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3.
Ghavami S, Eshragi M, Ande SR, Chazin WJ, Klonisch T, Halayko AJ, McNeill KD, Hashemi M, Kerkhoff C, Los M
(2010) Cell Res 20: 314-31
MeSH Terms: Adenine, Apoptosis, Autophagy, Autophagy-Related Protein 12, Autophagy-Related Protein 5, Calgranulin A, Calgranulin B, Cell Line, Humans, Lysosomes, Macrolides, Membrane Proteins, Microtubule-Associated Proteins, Mitochondria, Phosphatidylinositol 3-Kinases, Phosphoinositide-3 Kinase Inhibitors, Proto-Oncogene Proteins, Reactive Oxygen Species, Small Ubiquitin-Related Modifier Proteins, Vacuolar Proton-Translocating ATPases
Show Abstract · Added March 12, 2014
The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity in various cells of different origins. Here, we present evidence that the underlying molecular mechanisms involve both programmed cell death I (PCD I, apoptosis) and PCD II (autophagy)-like death. Treatment of cells with S100A8/A9 caused the increase of Beclin-1 expression as well as Atg12-Atg5 formation. S100A8/A9-induced cell death was partially inhibited by the specific PI3-kinase class III inhibitor, 3-methyladenine (3-MA), and by the vacuole H(+)-ATPase inhibitor, bafilomycin-A1 (Baf-A1). S100A8/A9 provoked the translocation of BNIP3, a BH3 only pro-apoptotic Bcl2 family member, to mitochondria. Consistent with this finding, DeltaTM-BNIP3 overexpression partially inhibited S100A8/A9-induced cell death, decreased reactive oxygen species (ROS) generation, and partially protected against the decrease in mitochondrial transmembrane potential in S100A8/A9-treated cells. In addition, either DeltaTM-BNIP3 overexpression or N-acetyl-L-cysteine co-treatment decreased lysosomal activation in cells treated with S100A8/A9. Our data indicate that S100A8/A9-promoted cell death occurs through the cross-talk of mitochondria and lysosomes via ROS and the process involves BNIP3.
0 Communities
1 Members
0 Resources
20 MeSH Terms
S100A8/A9: a Janus-faced molecule in cancer therapy and tumorgenesis.
Ghavami S, Chitayat S, Hashemi M, Eshraghi M, Chazin WJ, Halayko AJ, Kerkhoff C
(2009) Eur J Pharmacol 625: 73-83
MeSH Terms: Animals, Apoptosis, Calgranulin A, Calgranulin B, Epithelial Cells, Gene Expression Regulation, Neoplastic, Humans, Immunotherapy, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms
Show Abstract · Added March 12, 2014
Correlations exist between the abundance of S100 proteins and disease pathologies. Indeed, this is evidenced by the heterodimeric S100 protein complex S100A8/A9 which has been shown to be involved in inflammatory and neoplastic disorders. However, S100A8/A9 appears as a Janus-faced molecule in this context. On the one hand, it is a powerful apoptotic agent produced by immune cells, making it a very fascinating tool in the battle against cancer. It spears the risk to induce auto-immune response and may serve as a lead compound for cancer-selective therapeutics. In contrast, S100A8/A9 expression in cancer cells has also been associated with tumor development, cancer invasion or metastasis. Clearly, there is a dichotomy and future investigations into the role of S100A8/A9 in cancer biology need to consider both sides of the same coin.
0 Communities
1 Members
0 Resources
11 MeSH Terms
Identification of early intestinal neoplasia protein biomarkers using laser capture microdissection and MALDI MS.
Xu BJ, Li J, Beauchamp RD, Shyr Y, Li M, Washington MK, Yeatman TJ, Whitehead RH, Coffey RJ, Caprioli RM
(2009) Mol Cell Proteomics 8: 936-45
MeSH Terms: Adenoma, Animals, Biomarkers, Tumor, Calgranulin A, Case-Control Studies, Humans, Intestinal Neoplasms, Lasers, Mice, Microdissection, Neoplasm Proteins, Proteome, Proteomics, Reproducibility of Results, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Show Abstract · Added June 14, 2013
Obtaining protein profiles from a homogeneous cell population in tissues can significantly improve our capability in protein biomarker discovery. In this study, unique protein profiles from the top and bottom sections of mouse crypts and Apc(Min+/-) adenomas were obtained using laser capture microdissection (LCM) combined with MALDI MS. Statistically significant protein peaks with differential expression were selected, and a set of novel protein biomarkers were identified. Immunohistochemistry was performed to confirm the differentially expressed protein biomarkers found by LCM combined with MALDI MS. To validate the relevance of the findings in human colorectal cancer (CRC), S100A8 was further confirmed in human CRC using immunohistochemistry. In addition, S100A8 was found to have an increased expression at different human CRC stages (Duke's A-D) compared with controls at both protein (n = 168 cases) and RNA (n = 215 cases) levels. Overall LCM combined with MALDI MS is a promising method to identify intestinal protein biomarkers from minute amounts of tissue. The novel protein biomarkers identified from the top and bottom crypts will increase our knowledge of the specific protein changes taking place during cell migration from the crypt bottom to top. In addition, the identified cancer protein biomarkers will aid in the exploration of colorectal tumorigenesis mechanisms as well as in the advancement of molecularly based diagnosis of colorectal cancer.
2 Communities
5 Members
0 Resources
15 MeSH Terms
Free cholesterol accumulation in macrophage membranes activates Toll-like receptors and p38 mitogen-activated protein kinase and induces cathepsin K.
Sun Y, Ishibashi M, Seimon T, Lee M, Sharma SM, Fitzgerald KA, Samokhin AO, Wang Y, Sayers S, Aikawa M, Jerome WG, Ostrowski MC, Bromme D, Libby P, Tabas IA, Welch CL, Tall AR
(2009) Circ Res 104: 455-65
MeSH Terms: Adaptor Proteins, Vesicular Transport, Animals, Aorta, Apolipoproteins E, Calgranulin A, Cathepsin K, Cathepsins, Cell Membrane, Cells, Cultured, Cholesterol, E-Box Elements, Endosomes, Enzyme Induction, Humans, Intracellular Signaling Peptides and Proteins, Macrophages, Matrix Metalloproteinase 14, Matrix Metalloproteinase 8, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Knockout, Microphthalmia-Associated Transcription Factor, Phosphorylation, Promoter Regions, Genetic, Proteins, Receptor Activator of Nuclear Factor-kappa B, S100 Proteins, Signal Transduction, Time Factors, Toll-Like Receptor 3, Toll-Like Receptor 4, p38 Mitogen-Activated Protein Kinases, rab GTP-Binding Proteins
Show Abstract · Added December 10, 2013
The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c-Apoe(-/-) mice bearing a null mutation in the Npc1 gene display prominent medial erosion and atherothrombosis, whereas their macrophages accumulate free cholesterol in late endosomes and show increased cathepsin K (Ctsk) expression. We now show increased cathepsin K immunostaining and increased cysteinyl proteinase activity using near infrared fluorescence imaging over proximal aortas of Apoe(-/-), Npc1(-/-) mice. In mechanistic studies, cholesterol loading of macrophage plasma membranes (cyclodextrin-cholesterol) or endosomal system (AcLDL+U18666A or Npc1 null mutation) activated Toll-like receptor (TLR) signaling, leading to sustained phosphorylation of p38 mitogen-activated protein kinase and induction of p38 targets, including Ctsk, S100a8, Mmp8, and Mmp14. Studies in macrophages from knockout mice showed major roles for TLR4, following plasma membrane cholesterol loading, and for TLR3, after late endosomal loading. TLR signaling via p38 led to phosphorylation and activation of the transcription factor Microphthalmia transcription factor, acting at E-box elements in the Ctsk promoter. These studies suggest that free cholesterol enrichment of either plasma or endosomal membranes in macrophages leads to activation of signaling via various TLRs, prolonged p38 mitogen-activated protein kinase activation, and induction of Mmps, Ctsk, and S100a8, potentially contributing to plaque complications.
0 Communities
1 Members
0 Resources
34 MeSH Terms