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)

The S-100 proteins MRP-8 and MRP-14 are expressed by cells of the myelomonocytic lineage, either alone or simultaneously during certain stages of cellular differentiation. We demonstrate that MRP-14 but not MRP-8 was detected by immunostaining in the cytoplasm of epithelioid cells on the surface of round coverslips implanted for 14 days into the subcutaneous tissue of mice. Using this experimental model, our laboratory has previously shown that epithelioid macrophages are poor phagocytic cells that release a macrophage-deactivating factor (MDF) in short-term cultures. The full chemical characterization of MDF has not been achieved so far. We provide evidence that the calcium-binding protein MRP-14 was also released by epithelioid macrophages in short-term cultures and that its neutralization from the culture medium after addition of monoclonal antibody anti-MRP-14 abolished the MDF activity of the conditioned medium. Purified or recombinant human MRP-14 but not MRP-8 inhibits the respiratory burst of BCG-activated macrophages. Recombinant mouse MRP-14 also down-regulate macrophage activation in vitro, and PMA does not revert the inhibitory effect induced by MRP-14. It is thus concluded that epithelioid cells from foreign-body granuloma express and release MRP-14 in short-term cultures and that this molecule is endowed with MDF activity.
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PMID:Epithelioid cells from foreign-body granuloma selectively express the calcium-binding protein MRP-14, a novel down-regulatory molecule of macrophage activation. 940 Aug 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

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

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

MRP-8 and -14 are two S100 proteins highly expressed as a complex by neutrophils, and to a lesser extent by monocytes and certain squamous epithelia. However, less is known about the close homologue S100A12. This S100 protein is expressed by neutrophils and here we show that it is also expressed by monocytes, but not lymphocytes. An absence of coimmunoprecipitation of MRP-14 and S100A12 indicates that S100A12 is not associated with the MRP proteins in vivo. When directly compared to MRP-14, S100A12 expression by squamous epithelia is more restricted. In esophagus and psoriatic skin, S100A12 is differentially regulated, like MRP-14, but the expression pattern of the two S100 proteins is quite different.
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PMID:A comparison of human S100A12 with MRP-14 (S100A9). 1097 13

The S100 calcium-binding proteins MRP-8 (S100A8) and MRP-14 (S100A9) form a heterodimeric complex in the cytosol of monocyte and neutrophil cell types circulating in peripheral blood. This complex, but not the individual subunit proteins, is specifically recognized by mAb 27E10. Domains in MRP-8 and MRP-14 mediating heterodimeric complex formation have not yet been identified but it is predicted that the structure of the complex will be similar to homodimeric forms of other S100 proteins. This study makes use of the specificity of mAb 27E10, and an in vitro coupled transcription/translation system to further examine the formation and maintenance of the MRP-8/MRP-14 complex. Truncated mutants of MRP-14 that lack the N-terminal residues 1-4 or the extended C-terminal 'tail', both complex with MRP-8. These deleted domains of MRP-14 are therefore not essential for complex formation. Peptides from MRP-8 or MRP-14, used to induce the epitope recognized by mAb 27E10, show that a critical interaction in complex formation involves the N-terminal of MRP-8 interacting with MRP-14. Phage display analysis defined composite residues of the epitope recognized by mAb 27E10. The epitope is trans-subunit, composed of residues in the C-terminal ends of helix IV in MRP-14 and helix I of MRP-8. A further complex-specific mAb, named 5.5, recognizes the hydrophobic residues in helix IV of MRP-8, exposed during heterodimer formation. The definition of these two epitopes indicates that helices IV of MRP-8 and MRP-14 are also a prominent point of interaction and suggests that the subunit proteins will assume an antiparallel alignment in the heterodimer, similar in structure to the homodimeric forms of S100 proteins.
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PMID:The heterodimeric complex of MRP-8 (S100A8) and MRP-14 (S100A9). Antibody recognition, epitope definition and the implications for structure. 1116 70

By photoaffinity labeling with a tritiated azido derivative of phenylarsine oxide (PAO), 4[N-(4-azido-2-nitrophenyl)amino-[(3)H]acetamido]phenylarsine oxide ([(3)H]azidoPAO), we demonstrate that PAO binds selectively to the S100 A8/A9 complex of bovine neutrophil cytosol (previously known as p7/p23, homologous to the MRP-8/MRP-14 complex of human phagocytes). Using a semirecombinant cell free assay of oxidase activation and the determination of oxidase activity by the production of the superoxide anion O(-)(2), we found that the PAO binding protein (p7/p23) was able to potentiate the activation of NADH oxidase and that this effect was synergized by PAO. The p7/p23 protein complex of bovine neutrophils can therefore be considered as a positive regulator of NADPH oxidase activation in neutrophils.
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PMID:A phenylarsine oxide-binding protein of neutrophil cytosol, which belongs to the S100 family, potentiates NADPH oxidase activation. 1147 1

The S100 family proteins MRP-8 (S100A8) and MRP-14 (S100A9) form a heterodimer that is abundantly expressed in neutrophils, monocytes, and some secretory epithelia. In inflamed tissues, the MRP-8/14 complex is deposited onto the endothelium of venules associated with extravasating leukocytes. To explore the receptor interactions of MRP-8/14, we use a model system in which the purified MRP-8/14 complex binds to the cell surface of an endothelial cell line, HMEC-1. This interaction is mediated by the MRP-14 subunit and is mirrored by recombinant MRP-14 alone. The cell surface binding of MRP-14 was blocked by heparin, heparan sulfate, and chondroitin sulfate B, and the binding sites were sensitive to heparinase I and trypsin treatment but not to chondroitinase ABC. Furthermore MRP-8/14 and MRP-14 did not bind to a glycosaminoglycan-minus cell line. MRP-14 has a high affinity for heparin (K(d) = 6.1 +/- 3.4 nm), and this interaction mimicked that with the endothelial cells. We therefore conclude that the MRP-8/14 complex binds to endothelial cells via the MRP-14 subunit interacting chiefly with heparan sulfate proteoglycans. CD36 and RAGE, two other putative receptors for MRP-8/14, were not expressed by HMEC-1 cells. This binding activity may explain the immobilization of the MRP-8/14 complex on endothelium that is observed in vivo.
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PMID:The S100 family heterodimer, MRP-8/14, binds with high affinity to heparin and heparan sulfate glycosaminoglycans on endothelial cells. 1172 10

Following surgical removal of glioblastoma multiforme (GBM), radiochemotherapy impedes neoplastic outgrowth and relapse formation. Macrophages/microglial cells are believed to be potent mediators of the host defense system in GBM. However, little is known about their alteration by postsurgical therapies. We have now analyzed expression of LCA (leucocyte common antigen), CD68 (phagocytic cells), HLA-DR, -DP, -DQ (MHC class II), MRP-8 (myeloid-related protein, S100A8), MRP-14 (S100A9), LCF (lymphocyte chemoattractant factor, IL-16) and NOS II (inducible nitric oxide synthase) in macrophages/microglial cells in 39 GBM relapses and their matched primary tumors. Following surgery of the primary tumors, 15 patients received irradiation and chemotherapy, 17 irradiation and 7 no treatment. In irradiated relapses, we observed significantly more macrophages/microglial cells expressing MRP-14 compared to untreated GBM relapses. Furthermore, we observed a significant increase of CD68 expressing macrophages/microglial cells in patients without postsurgical treatment, but not in those with radiochemotherapy. In conclusion, our findings suggest that radiochemotherapy alters the number of MRP-14 expressing cells. The lacking increase of CD68 expressing cells in patients with radiochemotherapy suggests depletion of this cell type by postsurgical therapy.
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PMID:Macrophage/microglial cell subpopulations in glioblastoma multiforme relapses are differentially altered by radiochemotherapy. 1185 68

Excessive neutrophil recruitment is implicated in the pathogenesis of chronic lung diseases by causing collateral tissue damage. The cells move from the circulation in response to chemokines, such as interleukin (IL)-8, that are secreted by several lung cell types including epithelial cells. This study has investigated factors present in bronchial secretions that are responsible for IL-8 expression and secretion by epithelial cells and hence initiate or perpetuate the recruitment of neutrophils. A549 epithelial cells were stimulated with proinflammatory molecules likely to be of relevance in the lung. Tumor necrosis factor-alpha, IL-1beta, and lipopolysaccharide stimulated IL-8 production from epithelial cells in a dose- and time-dependent manner, and these effects were abrogated by specific antibodies or inhibitors. Bronchial secretions also stimulated IL-8 production, and lipopolysaccharide accounted for approximately 33% of this activity. An abundant 32-kD protein capable of stimulating IL-8 production was isolated from the secretion and identified as neutrophil cytoplasmic protein myeloid-related protein (MRP)-14, which is the heavy polypeptide chain in the MRP-8/14 heterodimer. Abrogation of MRP-14 activity with a specific antibody also reduced the IL-8-stimulating potential of bronchial secretions, suggesting it was a significant stimulus to IL-8 production in the lung and may amplify the neutrophilic inflammation seen in bronchial disease.
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PMID:Myeloid related protein-8/14 stimulates interleukin-8 production in airway epithelial cells. 1274 56


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