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)

Two associated calcium-binding proteins (CaBPs) have recently been identified specifically in cells of myeloid origin. These proteins have relative molecular masses (Mr) of 8,000 and 14,000 and are variously referred to as the cystic fibrosis antigen, the L1 light chain, MRP-8 or p8, and the L1 heavy chain, MRP14 or p14, respectively. The expression of p8 and p14 seems to be confined to a specific stage of myeloid cell differentiation, because both proteins are expressed in circulating neutrophils and monocytes but not in normal tissue macrophages. In chronic inflammatory conditions, however, such as rheumatoid arthritis, macrophages in affected tissues express both p8 and p14. These proteins are members of a family of CaBPs of low Mr, which include S-100 alpha and beta proteins, calcyclin (2A9), intestinal CaBP and p11. All the proteins have an Mr of approximately 10,000 with the exception of p14 which has a longer C-terminal sequence after the second calcium-binding domain. Little is known about their function, although by analogy with calmodulin they could be molecules involved in intracellular signalling that are activated by an increase in the intracellular Ca2+ concentration ([Ca2+]). Here we report that p14 is phosphorylated in both monocytes and neutrophils. The level of p14 phosphorylation can be increased by elevating the [Ca2+]i using the ionophore ionomycin, but is not affected by activation of protein kinase C using phorbol 12,13-dibutyrate. The phosphorylated residue is threonine at position 113, which is the penultimate amino acid in p14 and contained in the longer 'tail' sequence. Part of this sequence is identical to the neutrophil immobilizing factors NIF-1 and NIF-2, indicating that the phosphorylation event could have a role in the generation of NIF activity in the p14 protein.
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PMID:Ionomycin-regulated phosphorylation of the myeloid calcium-binding protein p14. 247 89

Using a monoclonal antibody to macrophage migration inhibition factor (MIF), two proteins were isolated from supernatants of Concanavalin A-stimulated human peripheral blood mononuclear cells which seem to have complexed to a third component carrying the MIF activity. They are therefore designated MIF-related proteins or MRP-8 and MRP-14 according to their apparent molecular weights. Partial amino acid sequences have been determined and their cDNA have been cloned and expressed in Escherichia coli. Both are calcium-binding proteins and MRP-8 seems to be largely homologous to the cystic fibrosis antigen (Dorin et al., 1987). Antisera were raised in the rabbit against the recombinant proteins and their expression in cells and tissues studied using immunohistological techniques. The proteins are only found in blood granulocytes and monocytes. In culture the number of positive monocytes sharply increased and then declined with time, suggesting that their expression is associated with early stages of monocyte/macrophage differentiation and absent from resident macrophages in all tested tissues. In acute inflammatory reactions, e.g. gingivitis, MRP-8 is never seen in the tissue, whereas MRP-14 is expressed by intravascular monocytes and perivascular macrophages. In contrast, in chronic inflammation, e.g. rheumatoid arthritis, MRP-8 is also expressed by macrophages in the tissue. From this it is concluded that MRP-8 and MRP-14 are expressed sequentially at defined stages of monocyte/macrophage differentiation and that dysregulation of this process in chronic inflammation is mirrored by the presence of MRP-8-positive macrophages in the tissue.
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PMID:Two calcium-binding proteins associated with specific stages of myeloid cell differentiation are expressed by subsets of macrophages in inflammatory tissues. 304 9

This paper reports further study of the identity and function of a protein shown to be elevated in serum from cystic fibrosis (CF) patients and clinically normal heterozygotes. Monoclonal antibodies, specifically recognizing the tentatively named cystic fibrosis antigen (CFAg), were produced. Immunoaffinity purification of CFAg from several sources revealed two components: 11 x 10(3) and 14 x 10(3) Mr protein. cDNA clones corresponding to each protein have been isolated. Data-base comparisons of the deduced amino acid sequences suggest that both genes encode related but distinct calcium-binding proteins. We propose the name calgranulin A and B, for the 11 x 10(3) and 14 x 10(3) Mr components, respectively. It is clear from the assignment of the calgranulin genes to chromosome 1 that neither is the product of the mutant CF gene, which maps to chromosome 7. We have used the monoclonal antibodies to study the tissue distribution of the two proteins in a wide-ranging immunohistological survey. Where possible the pattern of expression was confirmed by RNA blot analysis. Strong calgranulin expression in granulocytes was confirmed. In addition to myeloid cells, a restricted subset of normal stratified squamous epithelia were found to be calgranulin-positive. These included tongue, oesophagus and buccal cells, the last of which has been shown to have altered calmodulin activity in CF patients. Using indirect alkaline phosphatase staining, tissue sections of lung, pancreas and skin (normally considered sites where the CF defect is expressed) were not calgranulin-positive. However, by indirect immunofluorescence, nasal polyp sections showed weak patchy calgranulin expression in some epithelial cells, and stronger, higher frequency expression when such cells were briefly cultured.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression pattern of two related cystic fibrosis-associated calcium-binding proteins in normal and abnormal tissues. 326 95

The aetiology and cellular mechanism of chronic inflammatory processes are poorly understood. Macrophages act prominently in the inflammatory response and we report here that they express two calcium-binding proteins. The expression of these proteins, referred to as MRP-8 and MRP-14, is specific for cells of myeloid origin, namely granulocytes, monocytes and macrophages, and is observed in blood granulocytes and monocytes but not in normal tissue macrophages. In acutely inflamed tissues, macrophages can express MRP-14 but not MRP-8, and in chronic inflammations, such as primary chronic polyarthritis, infiltrate macrophages express both MRP-8 and MRP-14. Characterization of MRP-8 and MRP-14 could therefore be useful to the understanding of cellular processes induced in chronic inflammation.
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PMID:Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis. 331 57

Migration inhibitory factor-related protein 8 (MRP8) and MRP14, two S-100-like Ca(2+)-binding proteins, have been described in cells of the epithelial lineage where they are either expressed constitutively (e.g. by mucosal squamous epithelium) or induced during disease (e.g. in keratinocytes during the course of psoriasis). Their biological function, however, is not yet clear. Recent studies have provided evidence that S-100-like proteins may interact with cytoskeletal components; we have therefore studied the biochemical properties and subcellular distribution of MRP8 and MRP14 in epithelial cells. TR146 human squamous carcinoma cells, which were found to express MRP8 and MRP14 in Northern and Western blot studies, were chosen for analysis. Cross-linking experiments using bis(sulphosuccinimidyl)suberate followed by SDS/PAGE and Western blot analysis revealed formation of heteromeric MRP8-MRP14 complexes. On subjecting TR146 cell lysates to two-dimensional gel electrophoresis and Western blotting, four distinct MRP14 isoforms could be identified resembling those described earlier in macrophages. A differential centrifugation technique revealed a Ca(2+)-dependent translocation of MRP8-MRP14 from the cytoplasm to the membrane and the Nonidet P40-insoluble cytoskeletal fraction. Double-label immunofluorescence microscopy of Ca2+ ionophore A23187-stimulated TR146 cells and cytochalasin B and demecolcine cytoskeleton disruption studies identified these structures as keratin intermediate filaments. Ca(2+)-dependent binding of MRP8-MRP14 to keratin filaments was additionally confirmed by an in vitro binding assay. In conclusion, our data suggest that MRP8 and MRP14 may be involved in Ca(2+)-dependent reorganization of cytoskeletal filaments in epithelial cells, which could be of importance for events associated with differentiation and inflammatory activation.
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PMID:Increase of calcium levels in epithelial cells induces translocation of calcium-binding proteins migration inhibitory factor-related protein 8 (MRP8) and MRP14 to keratin intermediate filaments. 754 68

Cholesteatoma epithelium is characterised by a keratinocyte dysregulation with a hyperproliferative growth and altered differentiation. Keratinocytes with a reduced turnover time show an increase of calcium binding proteins like calgranulin A and B. These proteins are highly linked with the modulation of cell growth and differentiation. The expression of calgranulin A and B was studied immunohistochemically using the monoclonal antibody F12 on cryosections of cholesteatoma biopsies. Normal skin served as control. The staining in normal skin was confined to the highly proliferative activated follicular keratinocytes, whereas most cholesteatomas showed a staining of all cell layers of the epithelium. Our findings show that the keratinocyte dysregulation of the cholesteatoma epithelium is reflected by variations of the expression of calcium binding proteins.
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PMID:[Expression of calgranulin A and B in middle ear cholesteatoma]. 788 19

The S100 protein CP-10 (chemotactic protein, 10 kD), a potent chemotactic factor for murine and human polymorphonuclear cells (PMN) and murine monocytes, has been purified in small amounts from supernatants of activated murine spleen cells (Lackmann et al., 1992). To obtain a more abundant source of the protein, CP-10 was expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST). The property of S100 proteins to undergo calcium-dependent conformational changes was used in a novel approach to optimize the release of recombinant (r) CP-10 by thrombin cleavage. Purified rCP-10 was characterized by amino-terminal sequence analysis and bioassays. Optimal chemotactic activity of rCP-10 for murine PMN and WEHI-265 monocytoid cells was 10(-11) M (native protein has optimal chemotactic activity between 10(-11) and 10(-13) M). Immunization of rabbits with the GST/CP-10 fusion protein bound to glutathione-agarose beads resulted in high titer, specific antibodies that neutralized CP-10-initiated chemotaxis and were suitable for immunoblotting. A combination of Western and Northern analyses identified CP-10 in murine peritoneal exudate PMN and macrophages, splenocytes, bone marrow cells, and WEHI-265 cells (all of myeloid origin), but not in thymus, liver, lung, 3T3 fibroblasts, EL4 lymphoma cells, or bEND 3 brain endothelial cells, indicating cell-specific regulation of CP-10 expression.
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PMID:Recombinant and cellular expression of the murine chemotactic protein, CP-10. 817 23

1. Two small, abundant calcium-binding proteins were isolated from pig granulocytes. They were named p7A and p7B. Relative molecular masses were approx. 32,000 for p7A and 13,000 for p7B, when obtained by Sephadex G-75 gel filtration, while it was 7000 for both proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). 2. N-terminal sequence analysis suggests that p7A is homologous to human and mouse MRP-8 and that p7B may be related to human and mouse MRP-14, though some properties of the latter--such as mobility on SDS-PAGE--were found to be different. In addition, p7A and p7B could be resolved under native conditions, contrasting with the fact that human and mouse MRP-8/MRP-14 form noncovalent complexes.
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PMID:Isolation and N-terminal sequence of two low molecular weight calcium-binding proteins from pig granulocytes. 822 70

Myeloid calcium binding proteins MRP-8 and MRP-14 were induced, and their genes were coordinately expressed, during differentiation of human leukemia HL-60 cells into macrophage-like cells after treatment with 1,25-dihydroxyvitamin D3 (VD3). Both MRP-8 and MRP-14 mRNAs appeared on the day after VD3 treatment. Their level reached a peak on day 2, and then quickly declined. Nuclear factors that interact with the 5'-upstream regions of MRP-8 and MRP-14 genes were studied with gel mobility-shift assays. Two factors (MP8FI and MP8FII) that interacted with 379 bp (426-48 bp upstream from the transcription-initiation site of MRP-8 gene) and 67 bp (-47 - +20) DNA fragments, respectively, were found in the cells treated with VD3 for 1 day. MP8FI and MP8FII were present neither in the nuclei of untreated HL-60 cells, nor in the nuclei of the cells treated with VD3 for 6 days. Human monocytic leukemia THP-1 cells, which constitutively expressed MRP genes, had MP8FII but not MF8FI. MP8FII was found to interact with the 19-mer sequence located just upstream of the TATA box. Also, two factors that bound to the different upstream regions (-400 - -150 and -149 - +50) of MRP-14 gene were detected in the differentiated HL-60 cells. One of these, MP14FI, appeared on day 1, but on day 6 its concentration greatly decreased. The other, MP14FII, was found in greater quantity on day 6 than on day 1. MP14FI, but not MP14FII, was found in THP-1 cells. These factors may be involved in the expression of MRP-8 and MRP-14 genes in VD3-differentiated HL-60 cells.
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PMID:Appearance of nuclear factors that interact with genes for myeloid calcium binding proteins (MRP-8 and MRP-14) in differentiated HL-60 cells. 849 45

The L1 protein occurs at high concentrations in neutrophils, monocytes, certain reactive tissue macrophages, squamous mucosal epithelia, and reactive epidermis. It constitutes in fact about 60% of the neutrophilic cytosol protein fraction. The two L1 chains (L1H and L1L) are referred to by a bewildering collection of names, various authors having different preferences (MRP-8 and MRP-14; CFA or calgranulin A and B). The most recent proposal is calprotectin because of its calcium-binding properties and antimicrobial effect shown in vitro. L1 belongs to the S-100 protein family and may be involved in the regulation of keratinocyte proliferation and differentiation. It exists at high levels in blood and interstitial tissue fluid in several infectious, inflammatory, and malignant disorders, and it is released abundantly in foci of granulocytes and macrophages. The C-terminal sequence of the L1H chain has been shown to be identical to the N-terminus of peptides known as neutrophil immobilizing factors. Such an activity of L1 could be important for the accumulation of vital granulocytes, while L1 released from neutrophils, macrophages and epithelial cells might exert antimicrobial activity, perhaps by depriving microorganisms of zinc. The minimum inhibitory concentrations of L1 in vitro were found to be 4-32 mg/l for Candida albicans, 64 mg/l for Staphylococcus aureus, 64-256 mg/l for S. epidermidis, and 256 mg/ml for Escherichia coli and Klebsiella spp. Killing was observed at 2-4 times higher concentrations. In patients with HIV infection, those who developed oral candidiasis had significantly lower parotid L1 levels than those who did not (67 micrograms/l vs. 216 micrograms/l).
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PMID:The leucocyte protein L1 (calprotectin): a putative nonspecific defence factor at epithelial surfaces. 852 6


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