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 expression of inducible nitric oxide synthase (iNOS), major histocompatibility class II molecules (MHC-II), CD68, and the calcium-binding proteins S100A8 and S100A9 (also called MRP8 and MRP14, respectively) was assessed in lung tissues from cattle that succumbed to pneumonia. Expression patterns of these markers were related to the types of lung lesion. iNOS expression was only observed in lungs infected with Arcanobacterium pyogenes or Pasteurella haemolytica but not in lungs from cattle with subacute chronic interstitial pneumonia and acute interstitial pneumonia due to Escherichia coli infection. High levels of iNOS were expressed by cells (probably leukocytes) surrounding necrotic foci. Occasionally, iNOS was expressed by intraalveolar macrophages in viable parenchyma, by leukocytes within the airways, and by some chondrocytes in the supporting cartilage of bronchi. Cells expressing MHC-II were distributed relatively evenly throughout areas of inflammation and did not display any clear association with necrotic foci. Cell types expressing MHC-II included type II alveolar epithelial cells, spindle-shaped cells of the interstitium, cells in bronchus-associated lymphoid tissue, and leukocytes in lymph and blood vessels but largely excluded iNOS-positive cells. Likewise, CD68-positive cells were rarely positive for iNOS and were not confined to the areas surrounding necrotic tissue. As with MHC-II and CD68, there was little if any coexpression of iNOS and either of the S100 proteins tested. Thus, in cattle with necrotizing bronchopneumonia, iNOS-expressing cells were largely restricted to the cellular zone surrounding necrotic areas.
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PMID:Expression of inducible nitric oxide synthase in spontaneous bovine bronchopneumonia. 1049 Feb 7

The functional importance of members of the S100 Ca2+-binding protein family is becoming apparent. Murine (m)S100A8 (initially named CP-10) is a potent chemoattractant (10(-13) to 10(-11) M) for myeloid cells and the chemotactic activity of other S100s has since been reported, suggesting a new class of chemoattractants. Murine S100A8 has been associated with a number of acute and chronic inflammatory conditions including bacterial infection, atherogenesis, and cystic fibrosis. It is expressed constitutively with S100A9 in neutrophils and is regulated by inflammatory stimulants in macrophages and microvascular endothelial cells. The lack of co-expression of S100A9 with S100A8 in activated macrophages suggests distinct functions for the proteins expressed by different cell types. Glucocorticoids up-regulate induction of mS100A8 by inflammatory mediators, and its exquisite sensitivity to oxidation suggests that it may protect against oxidative tissue damage. Inactivation of the mS100A8 gene is embryonic lethal, providing the first evidence for non-redundant function of a member of the S100 gene family. S100A8 may have an immunoregulatory role by contributing to the regulation of fetal-maternal interactions. It may play a protective role and its absence may allow infiltration by maternal cells, a process eventually manifesting as resorption. This review focuses on the variety of emerging functions attributed to murine S100A8, a protein implicated in embryogenesis, growth, differentiation, and immune and inflammatory processes.
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PMID:S100A8: emerging functions and regulation. 1053 7

Recently, we identified the two myeloid related protein-8 (MRP8) (S100A8) and MRP14 (S100A9) as fatty acid-binding proteins (Klempt, M., Melkonyan, H., Nacken, W., Wiesmann, D., Holtkemper, U., and Sorg, C. (1997) FEBS Lett. 408, 81-84). Here we present data that the S100A8/A9 protein complex represents the exclusive arachidonic acid-binding proteins in human neutrophils. Binding and competition studies revealed evidence that (i) fatty acid binding was dependent on the calcium concentration; (ii) fatty acid binding was specific for the protein complex formed by S100A8 and S100A9, whereas the individual components were unable to bind fatty acids; (iii) exclusively polyunsaturated fatty acids were bound by S100A8/A9, whereas saturated (palmitic acid, stearic acid) and monounsaturated fatty acids (oleic acid) as well as arachidonic acid-derived eicosanoids (15-hydroxyeicosatetraenoic acid, prostaglandin E(2), thromboxane B(2), leukotriene B(4)) were poor competitors. Stimulation of neutrophil-like HL-60 cells with phorbol 12-myristate 13-acetate led to the secretion of S100A8/A9 protein complex, which carried the released arachidonic acid. When elevation of intracellular calcium level was induced by A23187, release of arachidonic acid occurred without secretion of S100A8/A9. In view of the unusual abundance in neutrophilic cytosol (approximately 40% of cytosolic protein) our findings assign an important role for S100A8/A9 as mediator between calcium signaling and arachidonic acid effects. Further investigations have to explore the exact function of the S100A8/A9-arachidonic acid complex both inside and outside of neutrophils.
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PMID:The two calcium-binding proteins, S100A8 and S100A9, are involved in the metabolism of arachidonic acid in human neutrophils. 1055 23

Analysis of the calcium-induced arachidonic acid (AA) binding to S100A8/A9 revealed that maximal AA binding was achieved at molar ratios of 1 mol S100A8 and 1 mol S100A9 and for values greater than 3 calciums per EF-hand. The AA binding capacity was not induced by the binding of other bivalent cations, such as Zn2+, Cu2+, and Mg2+, to the protein complex. In contrast, the binding of AA was prevented by the addition of either Zn2+ or Cu2+ in the presence of calcium, whereas Mg2+ failed to abrogate the AA binding capacity. The inhibitory effect was not due to blocking the formation of S100A8/A9 as demonstrated by a protein-protein interaction assay. Fluorescence measurements gave evidence that both Zn2+ and Cu2+ induce different conformational changes thereby affecting the calcium-induced formation of the AA binding pocket within the protein complex. Due to the fact that the inhibitory effect of Zn2+ was present at physiological serum concentrations, it is assumed that released S100A8/A9 may carry AA at inflammatory lesions, but not within the blood compartment.
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PMID:Zinc binding reverses the calcium-induced arachidonic acid-binding capacity of the S100A8/A9 protein complex. 1057 Oct 75

Our current results, aimed at the detection of protein abundance alterations that could be associated with the process of colon tumorigenesis, are summarized. The matched sets of macroscopically normal colon mucosa and colorectal carcinoma were examined by a one- or two-dimensional electrophoretic approach and proteins were identified using immunoblotting or mass spectrometry. The following results were observed: The levels of liver fatty acid-binding protein, actin-binding protein/smooth muscle protein 22-alpha and cyclooxygenase 2 were downregulated in colorectal carcinoma compared to normal colon mucosa. Conversely, the expression of a novel variant of heat shock protein70 and several members of the S100 protein family of calcium-binding proteins (two isoforms of S100A9, S100A8, S100A11 and S100A6) were upregulated in transformed colon mucosa. Despite the variations of the levels of expression of given protein among analyzed samples, all quantitative changes were found to be statistically significant (Mann-Whitney test assuming p < or = 0.05). We conclude that the proteomic approach is useful for the study of complex biological events underlying the process of colorectal tumorigenesis.
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PMID:Protein abundance alterations in matched sets of macroscopically normal colon mucosa and colorectal carcinoma. 1061 91

The intercellular tight junctions (TJs) of endothelial cells represent the limiting structure for the permeability of the blood-brain barrier (BBB). Although the BBB has been recognized as being the interface between the bloodstream and the brain, little is known about its regulation. Zonulin and its prokaryotic analogue, zonula occludens toxin (Zot) elaborated by Vibrio cholerae, both modulate intercellular TJs by binding to a specific surface receptor with subsequent activation of an intracellular signaling pathway involving phospholipase C and protein kinase C activation and actin polymerization. Affinity column purification revealed that human brain plasma membrane preparations contain two Zot binding proteins of approximately 55 and approximately 45 kDa. Structural and kinetic studies, including saturation and competitive assays, identified the 55-kDa protein as tubulin, whereas the 45-kDa protein represents the zonulin/Zot receptor. Biochemical characterization provided evidence that this receptor is a glycoprotein containing multiple sialic acid residues. Comparison of the N-terminal sequence of the zonulin/Zot receptor with other protein sequences by BLAST analysis revealed a striking similarity with MRP-8, a 14-kDa member of the S-100 family of calcium binding proteins. The discovery and characterization of this receptor from human brain may significantly contribute to our knowledge on the pathophysiological regulation of the BBB.
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PMID:Affinity purification and partial characterization of the zonulin/zonula occludens toxin (Zot) receptor from human brain. 1061 35

The murine calcium-binding protein S100A8 is a potent chemoattractant for neutrophils and monocytes in vivo and in vitro but may also play a protective role. We show that the kinetics of induction of S100A8 mRNA in elicited murine macrophages (Mac) by LPS, IFN-gamma, and TNF were distinct from the C-C chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage-inflammatory protein-1alpha (MIP-1alpha), and RANTES. Monomeric S100A8 was predominantly secreted. IFN substantially increased S100A8 mRNA levels after 1 h with optimal induction after 12 h; induction by TNF was slower and more sustained. TNF did not up-regulate MCP-1 and MIP-1alpha mRNA in these cells. Luciferase reporter assays confirmed that LPS and IFN induce S100A8 gene transcription and mRNA in LPS-treated Mac showed little decay over 16 h, whereas transcripts induced by IFN and TNF were markedly less stable. Newly synthesized proteins may be required for mRNA transcription and stabilization in response to LPS. S100A9 associates with A8 in neutrophils, but was not coinduced with S100A8. S100A8 gene induction in Mac stimulated with LPS and IFN may be modulated by mobilization of intracellular Ca2+ concentration from distinct intracellular stores and/or the extracellular compartment and by distinct pathways involving protein kinase C and leading to activation of mitogen-activated protein kinase.
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PMID:IFN-gamma and TNF regulate macrophage expression of the chemotactic S100 protein S100A8. 1077 2

The myeloid-related proteins MRP8 (S100A8) and MRP14 (S100A9), two members of the S100 family of calcium-binding proteins, are co-expressed and form a cell-surface and cytoskeleton-associated heterodimer upon calcium mobilization which is recognized by the mAb 27E10. The heterodimer is abundantly expressed in the cytoplasm of granulocytes and a subpopulation of blood monocytes. Previously, we and others demonstrated endothelium-associated MRP8/14 in inflamed tissues in the vicinity of transmigrating leukocytes, suggesting a function of the proteins in this process. Here, we demonstrate that 27E10(+) cells represent a fast-migrating monocyte subpopulation which preferentially utilizes an ICAM-1-dependent mechanism. The following observations imply a function of MRP8/14 in the transmigration process: (i) higher secretion of MRP8/14 from 27E10(+) monocytes compared to 27E10(-) monocytes after interaction with activated endothelium, (ii) higher expression of CD11b on 27E10(+) compared to 27E10(-) monocytes, (iii) up-regulation of CD11b on 27E10(-) monocytes in the presence of MRP14 or MRP8/14 heterodimers but not MRP8 and (iv) active participation of MRP14 but not of MRP8 in transmigration as shown by blocking with respective antibodies. We show that the interaction of 27E10(+) monocytes with activated endothelium leads to MRP8/14 release which may account for the high MRP8/14 concentrations in body fluids of patients with acute or chronic inflammatory diseases. Released MRP8/14 may serve a function by enhancing CD11b expression and/or affinity in human monocytes and by participating in the transendothelial migration mechanism. Thus, MRP8/14 substantially contributes to the recruitment of monocytes to an inflammatory site.
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PMID:Transendothelial migration of 27E10+ human monocytes. 1105 79

Intracellular calcium (Ca2+) has been shown to function as second messenger and to be associated with activation of different cell types including microglia. Previously, in human focal cerebral infarctions an early expression of macrophage-related protein-8 (MRP8/ S100A8), a member of the Ca2+-binding S100-protein family, in microglia has been reported. On the other hand, a delayed activation of microglia was observed following traumatic brain injury (TBI). We therefore examined immunohistochemically microglial expression of MRP8 and allograft inflammatory factor-1 (AIF-1), identical to microglial response factor-1 (mrf-1) and ionized calcium binding adaptor molecule-1 (ibal) in human brains after TBI and in control brains. Both, MRP8 and AIF-1 are Ca2+-binding peptides which have been associated with microglial activation in experimental models and in human cerebral infarctions. Detection of AIF-1 in controls confirmed constitutive expression of this peptide in a subset of microglial cells. After TBI, the density of AIF-1+ microglia did not increase significantly. Lesional expression of AIF-1 did not significantly differ from other brain regions. Furthermore, following TBI, we found no significant differences in the density of AIF-1+ microglia as compared to controls. Microglial MRP8 expression was not detectable in controls and within the first 3 days post TBI, but increased rapidly after 3 days post TBI, suggesting a subpopulation of microglial cells to be AIF-1-/MRP8+. We conclude that the delayed expression of MRP8 and the lack of AIF-1 up-regulation in microglia after TBI is in contrast to ischemic brain lesions and might reflect different activation cascades of microglia.
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PMID:Differential regulation of the monocytic calcium-binding peptides macrophage-inhibiting factor related protein-8 (MRP8/S100A8) and allograft inflammatory factor-1 (AIF-1) following human traumatic brain injury. 1107 14

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


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