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)

Leukocyte recruitment to inflammatory foci is generally associated with cellular activation. Recent evidence suggests that chemotactic agents can be divided into two classes, "classical chemoattractants" such as FMLP, C5a, and IL-8, which stimulate directed migration and activation events and "pure chemoattractants" such as TGF-beta 1 which influence actin polymerisation and movement but not oxidative burst and associated granular enzyme release. The studies reported here demonstrate that the murine S100 chemoattractant protein, CP-10, belongs to the "non-classical" group. Despite its potent chemotactic activity for neutrophils and monocytes/macrophages, CP-10 failed to increase [Ca2+]i in human or mouse PMN, although chemotaxis was inhibited by pertussis toxin, confirming the suggestion of a novel Ca(2+)-independent G-protein-coupled pathway for post-receptor signal transduction triggered by "pure chemoattractants." The co-ordinated up-regulation of Mac-1 and down-regulation of L-selectin induced by FMLP on human PMN in vitro was not observed with CP-10. Quantitative changes in immediate (30 s) actin polymerisation occurred with FMLP and CP-10-treated human PMN. The relative F-actin increases induced in WEHI 265 monocytoid cells by FMLP and CP-10 was optimal at 60 s and declined over 120 s. F-actin changes reflected the concentration and potencies of the agonists required to provoke chemotaxis. After 90 min, CP-10 profoundly altered cell shape and increased both cell size and F-actin within pseudopodia. These changes are typical of those mediating leukocyte deformability, and CP-10 may mediate leukocyte retention within microcapillaries and thereby contribute to the initiation of inflammation in vascular beds.
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PMID:S100 protein CP-10 stimulates myeloid cell chemotaxis without activation. 859 3

Chromosome 1 reveals in region 1q21 a most remarkable density of genes that fulfill important functions in terminal differentiation of the human epidermis. These genes encode the cornified envelope precursors loricrin, involucrin, and small proline-rich proteins (SPRR1, SPRR2, and SPRR3), the intermediate filament-associated proteins profilaggrin and trichohyalin, and several S100A calcium-binding proteins. Extending and refining our previous physical map of 1q21 we have now mapped two additional S100A genes as well as the three SPRR subfamilies and resolved the arrangement of involucrin, SPRRs, and loricrin. All genes are linked within 1.9 Mbp of human genomic DNA in the order: S100A10, trichohyalin, profilaggrin, involucrin, SPRR3, SPRR1B, SPRR2A, loricrin, S100A9, S100A9, S100A8, S100A6. Colocalization of genes expressed late during maturation of epidermal cells together with genes encoding calcium-binding proteins is particularly intriguing since calcium levels tightly control the differentiation of epithelial cells and the expression of genes encoding epidermal structural proteins. Accounting for the close functional cooperation among these structurally and evolutionary related genes, we conclude that these loci constitute a gene complex, for which we propose the name epidermal differentiation complex.
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PMID:Genes encoding structural proteins of epidermal cornification and S100 calcium-binding proteins form a gene complex ("epidermal differentiation complex") on human chromosome 1q21. 861 63

The myeloid-related proteins MRP-14 and MRP-8 and also p6, three calcium-binding proteins of the S100 family, translocate to the membrane during human neutrophil activation with stimuli known to require extracellular calcium for activity. When phorbol 12-myristate 13-acetate (PMA, an extracellular calcium-independent stimulus) is used, no translocation is observed. To characterize further the mechanisms involved in their translocation, phosphorylation of these proteins was studied. Three isoforms of MRP-14 were markedly phosphorylated in the membrane and in the cytosol upon activation with extracellular calcium-dependent stimuli, such as opsonized zymosan, the calcium ionophore A23187, N-formylmethionylleucylphenylalanine in the presence of cytochalasin B and arachidonic acid, or upon extracellular calcium-independent stimulation (PMA). In no case were p6 and a fourth, more basic isoform of MRP-14, phosphorylated. In PMA-activated cells, a phosphorylated acidic isoform of MRP-8 was detected in the cytosol only. However, phosphorylated MRP-8 represented only a small fraction of total MRP-8. Cgp 41251, an inhibitor of protein kinase C (PKC), completely inhibited the phosphorylation of MRP-8, and decreased cytosolic MRP-14 phosphorylation. To test whether phosphorylated MRP-8 could translocate, A23187, which induces translocation of the three S100 proteins, was added after PMA activation. This resulted in translocation of 18% +/- 5% of phosphorylated MRP-14 and 19% +/- 1% of only nonphosphorylated MRP-8. However, upon inhibition of PKC, translocation of MRP-14 and MRP-8 was increased up to 38% +/- 7% and 34% +/- 3% respectively. This suggests a putative role of phosphorylation and/or of PKC in the modulation of MRP-14 and MRP-8 translocation to the membrane.
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PMID:Phosphorylation of myeloid-related proteins MRP-14 and MRP-8 during human neutrophil activation. 889 15

Mac 387, a murine mAb, was previously described to detect a complex form of MRP-14 and MRP-8, two calcium-binding proteins of the S100 family, but recent experiments suggested that Mac 387 recognized only MRP-14. Using two-dimensional polyacrylamide gel electrophoresis and the very sensitive enhanced chemiluminescence detection system, the immunoreactivity of Mac 387 was compared with that of a polyclonal antibody raised against purified MRP-8, but cross-reacting with MRP-14 and p6, a novel S100 protein. Under such conditions, Mac 387 was found to recognize the three S100 proteins. This result suggests that Mac 387 might recognize an epitope common of the proteins of the S100 family.
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PMID:The monoclonal antibody Mac 387 recognizes three S100 proteins in human neutrophils. 893 61

We developed a quantitative enzyme immunoassay for human MRP-8/MRP-14, neutrophil cytosolic proteins with calcium-binding and bacteriastatic properties. MRP-8/MRP-14 concentrations were measured in the plasma of 23 healthy volunteers and in 75 patients with hematological disorders. These proteins were detected in plasma of healthy blood donors with mean +/- standard deviation 167 +/- 114 ng/ml. MRP-8/MRP-14 plasma levels ranged from 435 to 13280 ng/ml in patients with chronic myeloid leukemia (CML), from 50 to 7570 ng/ml in chronic lymphoid leukemia (CLL), from 450 to 2790 ng/ml in polycythemia vera (PV), and were significantly higher than in healthy blood donors (P < 0.01 for CML and P < 0.05 for others). In CML patients MRP-8/MRP-14 levels strongly correlated with total blood WBC count (r = 0.82) and with neutrophilic granulocyte (NG) count (r = 0.80). Correlation of these values in PV amounted to r = 0.70 and r = 0.46, respectively. In CLL patients MRP-8/MRP-14 levels strongly correlated with total WBC count (r = 0.92), but not with the NG count. We suggest that MRP-8/MRP-14 quantitation may serve as a marker of neutrophil pool turnover in some hematological disorders.
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PMID:Enzyme-linked immunosorbent assay for human MRP-8/MRP-14 proteins and their quantitation in plasma of hematological patients. 896 12

Here, we report the characterization of a human cDNA coding for the recently published amino acid sequence of a calcium-binding S100 protein, S100A12 (CGRP, calgranulin C, CAAF1, p6). The exon/intron structure of the S100A12 gene is similar to most other S100 genes. It is composed of three exons which are divided by two introns of 900 bp and 400 bp. The protein is encoded by sequences in exons 2 and 3, with exon 2 coding for the N-terminal 45 amino acids and exon 3 coding for the C-terminal 46 amino acids. So far, ten S100 genes are known to be located on human chromosome 1q21 in a clustered organization. Hence, we investigated whether S100A11 (S100C, calgizzarin) and S100A12 are also localized in the S100 gene cluster. We found both genes within the cluster, with S100A11 being close to S100A10 and S100A12 between the genes S100A8 and S100A9. Therefore, the S100 gene cluster now is composed of 12 differentially expressed family members.
Cell Calcium 1996 Dec
PMID:Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21. 898 90

So far, microglial activation in cerebral ischemia has only been studied in different animal models. We have investigated the activation of microglial cells in human cerebral ischemia. As a marker for the activation of these "brain macrophages," we have used the macrophage inhibitor factor-related-proteins MRP-8 and MRP-14, which belong to the calcium binding S-100 protein family. The proteins can be detected on microglial cells in bacterial encephalitis and Alzheimer's disease but have so far not been studied in non-inflammatory diseases, in which microglial activation also occurs. Antibodies against MRP-8 and -14 detected ramified microglial cells within the first 3 days after cerebral infarction. Labeled cells were found selectively in the periinfarctional area. To support the notion that these cells belong to the locally activated resident microglial population, we studied their proliferation rate by staining the Ki-67 antigen with the antibody MIB-1. Double-labeling clearly showed that in the early phase of cerebral infarction microglial cells in the periinfarctional area express MRP-8 and -14 and also proliferate. Surprisingly, MRPs are expressed no longer than 3 days post infarction. This indicates that the activation of the resident microglia is an early step of tissue reaction after cerebral infarction. Additionally, we found evidence that microglial cells contribute to the population of phagocytes only during the first 3 days post infarction. The majority of lipid phagocytes found in the later stages are obviously recruited from the blood-borne macrophage pool.
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PMID:Expression of the S-100 proteins MRP-8 and -14 in ischemic brain lesions. 898 65

The expression of inducible nitric oxide synthase (iNOS) was studied in the brains of cattle, sheep, and goat that succumbed to a natural infection with Listeria monocytogenes. The lesions in infected brains are characterized by microabscesses, perivascular cuffs, gliosis, glial nodules, and large areas of malacia. Using immunocytochemistry, we detected bacteria in microabscesses, particularly in sheep and goats, and in areas without signs of inflammation, but not in perivascular infiltrates. iNOS was expressed by macrophage (Mphi)-type cells of microabscesses and glial nodules but rarely by Mphi in areas of malacia, as determined by immunohistochemistry with iNOS-specific antibodies. iNOS was not detected in perivascular cuffs. Major histocompatibility complex class II molecules (MHC-II), another marker of cell activation, showed a different pattern of distribution. Perivascular cuffs contained high numbers of MHC-II-positive cells, including some with Mphi characteristics. Microabscesses in sheep and goats showed low expression of MHC-II, particularly in iNOS-expressing cells. In cattle, the expression of markers for activated or recruited phagocytes, the calcium-binding proteins S100A8 and S100A9 (formerly called MRP-8 and MRP-14, respectively), was largely restricted to cells showing weak or undetectable iNOS expression; iNOS-positive Mphi showed a low expression of S100A8 and S100A9. Thus, iNOS is expressed by a restricted subset of Mphi in listeric encephalitis. In cultured sheep and goat Mphi, a low proportion of cells expressed iNOS upon activation by L. monocytogenes and gamma interferon, resulting in nitrite generation at least 1 order of magnitude lower than that in similarly treated cattle Mphi. Since these species differences were much less obvious in vivo, it appears that the well-known species variation in iNOS expression by Mphi could reflect an in vitro phenomenon.
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PMID:Comparison of inducible nitric oxide synthase expression in the brains of Listeria monocytogenes-infected cattle, sheep, and goats and in macrophages stimulated in vitro. 939 27

The 14-kDa myeloid-related protein (MRP-14) and its heterodimeric partner, MRP-8, are members of the S100 family of calcium-binding proteins (S100A9 and S100A8, respectively). Their importance in neutrophil function is implied by their unusual abundance in neutrophil cytosol (approximately 40% of cytosolic protein). Previous work from our laboratory has demonstrated the extracellular association of these proteins with vascular endothelium adjacent to transmigrating leukocytes. We report here a function for MRP-14 as a stimulator of neutrophil adhesion mediated by the beta 2 integrin, Mac-1. MRP-14 is an affinity regulator of Mac-1 because it promotes binding of soluble ligand and expression of an "activation reporter" epitope of high affinity beta 2 integrins recognized by mAb24. The activity of MRP-14 is confined to regulating integrin function because, unlike other inflammatory agonists, there was no release of L-selectin, up-regulation of cytosolic Mac-1, or induction of neutrophil respiratory burst or calcium flux. Furthermore, MRP-14 does not act as a chemoattractant or cause alterations in cell shape or cytoskeleton. MRP-8 has a regulatory role in MRP-14 activity, inhibiting the adhesion induced by MRP-14 through the formation of the heterodimer. In terms of mechanism of action, MRP-14 does not increase Mac-1 function by direct binding to this integrin but recognizes a distinct receptor on neutrophils. This receptor interaction is pertussis toxin sensitive, indicating that MRP-14-generated signals leading to a Mac-1 affinity increase are heterotrimeric G protein dependent. We postulate that MRP-14 and MRP-8 are important in vivo candidates for the regulated adhesion of neutrophils through control of Mac-1 activity.
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PMID:The human S100 protein MRP-14 is a novel activator of the beta 2 integrin Mac-1 on neutrophils. 957 May 63

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


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