Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human oncodevelopmental protein (ODP) with a molecular size of 28 kDa was isolated, employing malignant ascitic fluid of an advanced mixed mesodermal tumor of the uterus, by anti-ODP coupled Affi-Gel 10 column chromatography, followed by preparative PAGE. The final preparation obtained with this procedure gave a single band exhibiting reactivity with an anti-ODP antibody on analytical sodium dodecyl sulfate-PAGE. The sequence of the first 20 N-terminal amino acids of this protein is identical with those of both the cystic fibrosis protein and Ca-binding protein MRP8 except at position 17, for which no result was obtained. Sequence analysis suggested that the protein shows 90% sequence homology with both these proteins.
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PMID:Isolation of an ascitic oncodevelopmental protein exhibiting high sequence homology with calcium-binding protein MRP8. 769 42

The murine S100 protein CP-10 is a potent chemotactic factor for murine and human myeloid cells in vivo and in vitro. This is the first report describing regulations of the CP-10 gene by a proinflammatory stimulus, lipopolysaccharide (LPS), in cells of the monocyte/macrophage lineage. Murine monocyte/macrophage-like WEHI 265 and RAW 264.7 cells preexposed to 5 to 50 ng/mL LPS expressed significant levels of CP-10 mRNA 4 hours, and maximal at 20 hours, after a secondary LPS challenge. This was accompanied by increasing levels of cell-associated and released CP-10 protein. In contrast, a single dose of LPS upregulated CP-10 mRNA in elicited peritoneal macrophages, whereas mRNA and protein levels decreased following LPS challenge. The state of macrophage differentiation may control responsiveness as LPS had no effect on CP-10 basal levels in bone marrow derived macrophages. LPS-induced CP-10 expression was controlled at the transcriptional level and nuclear run-on and protein synthesis inhibition assays indicated that LPS priming and challenge of RAW cells occurred via distinct pathways. MRP14, another S100 protein generally coordinately expressed with human MRP8, was not induced by LPS under the same conditions. We propose that CP-10 may play a key role in recruitment of leukocytes into tissues in response to gram-negative bacterial infection.
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PMID:Induction of the chemotactic S100 protein, CP-10, in monocyte/macrophages by lipopolysaccharide. 861 21

We found by using a 45Ca2+ overlay technique a large amount of Ca(2+)-binding activity in bovine amniotic fluid from which a novel calcium-binding protein (CaBP) was purified and is referred to as CAAF1 (calcium-binding protein in amniotic fluid-1), with an apparent molecular mass of 8 kDa determined by N-tris(hydroxymethyl)-methylglycine/ SDS-PAGE. It was structurally homologous with MRP/calgranulin proteins (MRP8/calgranulin A and MRP14/calgranulin B), members of the S100 protein family, which are abundantly found in the cytoplasm of granulocytes and macrophages. CAAF1 lacked the predicted signal peptide sequence, which is consistent with other CaBPs. The tissue and cellular distribution of CAAF1 was determined by monoclonal antibodies developed against this protein. Its immunoreactivity was found in squamous epithelial cells, neutrophils, and some macrophages throughout the fetal body. An especially characteristic staining pattern was obtained in the squamous epithelium, including that of the esophagus, skin and amnion: CAAF1 was detected in the suprabasal squamous epithelial cells undergoing differentiation, but not in the cells in the proliferating basal layer. Northern blot analysis also showed that CAAF1 mRNA was highly expressed in bovine fetal esophagus and skin. On the other hand, our ELISA studies showed that CAAF1 protein was present in amniotic fluid at a concentration of about 120 nM, which was over 30 times as high as that in the fetal serum. These results suggested that CAAF1 is one of the stage-specific proteins in the differentiation of squamous epithelial cells, and that CAAF1 is preferentially produced by fetal squamous epithelial cells, including epidermal keratinocytes and amniotic epithelial cells, and it is stored in the amniotic fluid during embryogenesis.
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PMID:A novel calcium-binding protein in amniotic fluid, CAAF1: its molecular cloning and tissue distribution. 871 72

Cellular characterization of the 91kDa-ectopic ascitic protein that exhibits pregnancy-associated and tumour-related dynamics has been examined in the human placenta using an electron microscopic immunocolloidal-gold technique. This protein was initially isolated from the ascitic fluids of a patient suffered from ovarian and uterine cancers with mixed mesodermal tumours, and determined to be sharing antigenicity with the 28kDa-oncodevelopmental protein and a calcium-binding protein; MRP8/CFA, respectively. Placentas obtained were divided into three groups by their gestational periods. Small chorionic villous tissues were embedded in Lowicryl K4M resin or Epon 812 resin. Specific and higher labelings by gold-particles were obtained in sections of Lowicryl resin and, then, recognized in mesenchyme-derived cells and/or myeloid lineages; such as placental tissue macrophages (Hofbauer cells), fibroblasts, foetal myelomonocytic cells including endothelial cells, etc., in the first and second trimesters. So far, the pattern of antigenic appearances changed depending on the stage of gestation. On the other hand, 91kDa-protein was also determined in the syncytiotrophoblast, but not in cytotrophoblasts at whenever been examined. It is assumed that the antigenic expression in syncytiotrophoblasts might be reflected to be absorbed or incorporated from those of foetal or maternal origins, and the antibody used in this study should be sensitive to the antigenic epitope derived from those of myeloid lineages. In the light of these results, hypotheses concerning mechanisms of both transplacental permeability of substances by the placental barrier and cell/tissue differentiation by calcium-binding (and/or -depending) proteins such as 91kDa-protein, MRP8, etc.; presumable the S-100 protein family, are discussed further.
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PMID:Cellular characterization of the 91kDa-ectopic ascitic antigen sharing antigenicity with MRP8 in the human placenta as revealed by immunoelectron microscopical colloidal-gold techniques. 958 13

The migration inhibitory factor-related proteins (MRPs) MRP-8 and MRP-14 were detected in differentiated human leukemia cell lines (THP-1 and HL-60) by immunocytochemical analysis. They were induced and colocalized in the cytoplasm and in lesser amounts in the nucleus when THP-1 and HL-60 cells were induced to differentiate by 1alpha,25-dihydroxyvitamin D3 or retinoic acid. In a search for a protein capable of binding MRPs, both MRPs were individually produced in insect cells (Sf21) infected with recombinant baculovirus. The purified recombinant MRPs were electrophoretically and antigenically indistinguishable from the native proteins, and their ability to form the MRP8/14 complex was retained. The presence of MRP binding sites was investigated by a binding assay using recombinant MRPs and specific monoclonal antibodies. MRP binding sites were detected on the cell membrane of the human leukemia cell lines THP-1, Raji, and MOLT-4. HL-60 cells treated with 1alpha, 25-dihydroxyvitamin D3 did not express MRP binding sites on the cell membrane, but a high level of MRPs accumulated in the cells. The occurrence of MRP binding sites on the cell surface of leukemia cell lines of monocyte and lymphocyte origin suggests that MRPs, released from neutrophils under certain conditions, may contribute to the activation and recruitment of effector cells to inflammatory lesions.
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PMID:Intracellular localization of migration inhibitory factor-related protein (MRP) and detection of cell surface MRP binding sites on human leukemia cell lines. 960 96

Human cerebral malaria (CM) is an often fatal infection. The cascades of signaling events resulting in tissue trauma and coma are only slowly becoming unraveled. Here we report that microglial cells--sensitive cellular sensors of threats to the central nervous system--in CM express the myeloid-related proteins MRP8 (S100A8) and MRP14 (S100A9), Ca2+-binding sensor proteins of activated monocytes. Surprisingly, microglial activation was widespread throughout the brain in white and gray matter and not limited to areas of petechial bleedings or sequestration of infected erythrocytes. Further, apoptosis/necrosis is prominent in CM; not only leukocytes appeared apoptotic, neurons also appeared damaged and DNA fragmentation was revealed by in situ nick translation. Thus, a prominent feature of human CM is activation of microglia, and analysis of these reactive microglia might further promote our understanding of CM pathology and guide development of future therapeutic intervention of the local reactive processes.
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PMID:Widespread expression of MRP8 and MRP14 in human cerebral malaria by microglial cells. 984 87

Calcium-binding S100 proteins are thought to play a central role in calcium-mediated signal transduction pathways. They consist of two helix-loop-helix, calcium-binding EF-hand domains. A characteristic feature is their tendency to form homo- and/or heterodimeric complexes. This report presents for the first time a functional "in vivo" approach to the analysis of S100 protein dimerization. Using the two-hybrid system we analyzed the dimerization of MRP8 (S100A8) and MRP14 (S100A9), two S100 proteins expressed in myeloid cells. It is reported that the MRP8-MRP14 heteromer is the clearly preferred complex in both man and mouse. The ability to homodimerize, however, appears to be restricted to the murine MRPs. Interaction analysis of chimeric murine/human MRP14 proteins indicates, that the C-terminal EF-hand domain plays a prominent role in MRP8-MRP14 interaction and determines the specificity of dimerization. Site-directed mutagenesis of four evolutionary conserved hydrophobic amino acids, which have been recently supposed to be essential for S100 protein dimerization, suggests that at least one of these, namely the most N-terminal located residue, is not critical for dimerization.
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PMID:Analysis of the MRP8-MRP14 protein-protein interaction by the two-hybrid system suggests a prominent role of the C-terminal domain of S100 proteins in dimer formation. 986 28

The two migration inhibitory factor- (MIF)-related protein-8 (MRP8; S100A8) and MRP14 (S100A9) are two calcium-binding proteins of the S100 family. These proteins are expressed during myeloid differentiation, are abundant in granulocytes and monocytes, and form a heterodimeric complex in a Ca2+-dependent manner. Phagocytes expressing MRP8 and MRP14 belong to the early infiltrating cells and dominate acute inflammatory lesions. In addition, elevated serum levels of MRP8 and MRP14 have been found in patients suffering from a number of inflammatory disorders including cystic fibrosis, rheumatoid arthritis, and chronic bronchitis, suggesting conceivable extracellular roles for these proteins. Although a number of possible functions for MRP8/14 have been proposed, the biological function still remains unclear. This review addresses recent developments regarding the MRP14-mediated promotion of leukocyte-endothelial cell-interactions and the characterization of MRP8/14 heterodimers as a fatty acid binding protein complex. In view of the current knowledge, the authors will hypothesize that MRP8 and MRP14 play an important role in leukocyte trafficking, but do not affect neutrophil effector functions.
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PMID:Novel insights into structure and function of MRP8 (S100A8) and MRP14 (S100A9). 992 Apr 11

S100A8 (also known as CP10 or MRP8) was the first member of the S100 family of calcium-binding proteins shown to be chemotactic for myeloid cells. The gene is expressed together with its dimerization partner S100A9 during myelopoiesis in the fetal liver and in adult bone marrow as well as in mature granulocytes. In this paper we show that S100A8 mRNA is expressed without S100A9 mRNA between 6.5 and 8. 5 days postcoitum within fetal cells infiltrating the deciduum in the vicinity of the ectoplacental cone. Targeted disruption of the S100A8 gene caused rapid and synchronous embryo resorption by day 9. 5 of development in 100% of homozygous null embryos. Until this point there was no evidence of developmental delay in S100A8-/- embryos and decidualization was normal. The results of PCR genotyping around 7.5-8.5 days postcoitum suggest that the null embryos are infiltrated with maternal cells before overt signs of resorption. This work is the first evidence for nonredundant function of a member of the S100 gene family and implies a role in prevention of maternal rejection of the implanting embryo. The S100A8 null provides a new model for studying fetal-maternal interactions during implantation.
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PMID:A null mutation in the inflammation-associated S100 protein S100A8 causes early resorption of the mouse embryo. 1043 63

Changes in cytosolic calcium concentrations regulate a wide variety of cellular processes, and calcium-binding proteins are the key molecules in signal transduction, differentiation, and cell cycle control. S100A12, a recently described member of the S100 protein family, has been shown to be coexpressed in granulocytes and monocytes together with two other S100 proteins, MRP8 (S100A8) and MRP14 (S100A9), and a functional relationship between these three S100 proteins has been suggested. Using Western blotting, calcium overlays, intracellular flow cytometry, and cytospin preparations, we demonstrate that S100A12 expression in leukocytes is specifically restricted to granulocytes and that S100A12 represents one of the major calcium-binding proteins in these cells. S100A12, MRP8, and MRP14 translocate simultaneously from the cytosol to cytoskeletal and membrane structures in a calcium-dependent manner. However, no evidence for direct protein-protein interactions of S100A12 with either MRP8 or MRP14 or the heterodimer was found by chemical cross-linking, density gradient centrifugation, mass spectrometric measurements, or yeast two hybrid detection. Thus, S100A12 acts individually during calcium-dependent signaling, independent of MRP8, MRP14, and the heterodimer MRP8/MRP14. This granulocyte-specific signal transduction pathway may offer attractive targets for therapeutic intervention with exaggerated granulocyte activity in pathological states.
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PMID:S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14. 1046 53


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