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)

Serum concentrations of two macrophage-derived calcium-binding proteins, MRP-8 and MRP-8/14, were studied in 28 patients with relapsing multiple sclerosis (MS). Serum levels were determined with a commercially available sandwich ELISA and the one-tailed Mann-Whitney U test was used for statistical analysis. Median serum levels of MRP-8/14 were significantly higher in MS patients (5150 ng/ml) compared to 26 healthy controls (1482 ng/ml) and significantly higher in MS patients within an acute relapse (6690 ng/ml) compared to MS patients with stable disease (3050 ng/ml). MRP-8 levels were not elevated in MS patients. These results may indicate an early activation of macrophages in the formation of demyelinating MS plaques. In addition, increased serum levels of MRP-8/14 may prove to be a useful paraclinical disease activity parameter in MS patients.
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PMID:Serum levels of macrophage-derived protein MRP-8/14 are elevated in active multiple sclerosis. 965 26

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

S100 Ca2+-binding proteins became of major interest because of their differential expression in tissues and their association with human diseases. Earlier studies showed that 13 S100 genes are located as a cluster on human chromosome 1q21. Since a number of mouse S 100 genes, such as S100A4 and S100A6, have been localized to a syntenic region on mouse chromosome 3, we investigated if the S100 gene cluster exists in mouse and is structurally conserved during evolution. First we identified the cDNA sequences of mouse S100A1, S100A3 and S100A5. Then we isolated a 490 kb mouse YAC clone which gives a specific signal by FISH most likely on chromosome 3. Hybridization studies with different mouse S100 cDNAs revealed that eight mouse S100 genes are arranged in a clustered organization similar to that in human. The linkage relationships between the genes S100A8-S100A9 and S100A3-S100A4-S100A5-S100A6 were conserved during divergence of human and mouse about 70 million years ago. However, the separation of the mouse S100 genes S100A1 and S100A13 in comparison to the human linkage group suggests rearrangement processes between human and mouse. Our data demonstrate that the S100 gene cluster is structurally conserved during evolution. Further studies on the genomic organization of the S100 genes including various species could generate new insights into gene regulatory processes and phylogenetic relationships.
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PMID:Clustered organization of S100 genes in human and mouse. 992 Apr 16

Chronic inflammatory discoid lupus erythematosus (DLE) and Jessner's lymphocytic infiltration of the skin (LIS) are both characterized by dermal infiltrates of activated T lymphocytes. However, an inflammatory involvement of the epidermis is only found in DLE. We therefore compared the phenotypic properties of the keratinocytes using immunohistochemical stainings of biopsies from typical DLE and LIS. Keratinocytes failed to express HLA-DR in LIS and surprisingly also in DLE. The adhesion molecule ICAM-1 was only expressed in DLE, with focal staining of the basal keratinocytes in close association with intraepidermal lymphocytes. The monoclonal antibody 27E10, a distinct marker for macrophage activation and differentiation, revealed a strong band-like labelling of the suprabasal and upper keratinocytes in DLE. In contrast, no epidermal expression of this biologically active heterodimer of the calcium-binding proteins MRP-8 and MRP-14 was found in LIS. The staining patterns provide a new method to differentiate DLE and LIS by immunohistochemistry and suggest a distinct type of keratinocyte activation and differentiation in DLE which would in turn mediate epidermal T cell infiltration.
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PMID:Macrophage marker 27E10 on human keratinocytes helps to differentiate discoid lupus erythematosus and Jessner's lymphocytic infiltration of the skin. 1006 57

The myeloid cell-derived calcium-binding murine protein, S100A8, is secreted to act as a chemotactic factor at picomolar concentrations, stimulating recruitment of myeloid cells to inflammatory sites. S100A8 may be exposed to oxygen metabolites, particularly hypochlorite, the major oxidant generated by activated neutrophils at inflammatory sites. Here we show that hypochlorite oxidizes the single Cys residue (Cys41) of S100A8. Electrospray mass spectrometry and SDS-polyacrylamide gel electrophoresis analysis indicated that low concentrations of hypochlorite (40 microM) converted 70-80% of S100A8 to the disulfide-linked homodimer. The mass was 20,707 Da, 92 Da more than expected, indicating additional oxidation of susceptible amino acids (possibly methionine). Phorbol 12-myristate 13-acetate activation of differentiated HL-60 granulocytic cells generated an oxidative burst that was sufficient to efficiently oxidize exogenous S100A8 within 10 min, and results implicate involvement of the myeloperoxidase system. Moreover, disulfide-linked dimer was identified in lung lavage fluid of mice with endotoxin-induced pulmonary injury. S100A8 dimer was inactive in chemotaxis and failed to recruit leukocytes in vivo. Positive chemotactic activity of recombinant Ala41S100A8 indicated that Cys41 was not essential for function and suggested that covalent dimerization may structurally modify accessibility of the chemotactic hinge domain. Disulfide-dependent dimerization may be a physiologically significant regulatory mechanism controlling S100A8-provoked leukocyte recruitment.
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PMID:Oxidation regulates the inflammatory properties of the murine S100 protein S100A8. 1008 90

CP-10 (chemotactic protein of m.w. 10,000) is a member of the S100 superfamily of Ca2+ binding peptides, which has potent chemotactic activity for murine and human myeloid cells. Here we report on the generation of monoclonal antibodies against CP-10 and accumulation of CP-10+ cells during experimental autoimmune encephalomyelitis (EAE), neuritis (EAN), uveitis (EAU) and in experimentally transplanted C6 gliomas. During acute inflammation, CP-10 is mainly expressed by large ED1+ monocytic perivascular cells that accumulate at days 11-14. CP-10+ cells are predominantly located in areas of cellular infiltration but are as well found in the meninges and infiltrating the brain parenchyma. In transplanted gliomas, CP-10+ cells are located exclusively within the tumor parenchyma. Using double labeling experiments, other cells participating in the inflammatory reaction were found to express CP-10, like few lymphoblastic W3/13+ cells in the vicinity of the inflammatory infiltrate.
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PMID:CP-10, a chemotactic peptide, is expressed in lesions of experimental autoimmune encephalomyelitis, neuritis, uveitis and in C6 gliomas. 1037 79

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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