The calcium‐binding proteins MRP8 and MRP14 form a membrane‐associated heterodimer in a subset of monocytes/macrophages present in acute but absent in chronic inflammatory lesions

Rs, Bhardwaj; Zotz, C; Zwadlo‐Klarwasser, G.; Roth, Johannes; Goebeler, Matthias; Mahnke, Karsten; Falk, Martina; Meinardus‐Hager, Georg; Sorg, Clemens

doi:10.1002/eji.1830220732

Cited by 186 publications

(145 citation statements)

References 38 publications

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“…The MRP8/ 14 heterodimer was immunolocalized by means of the monoclonal antibody 27E 10 which exclusively recognizes the MRP8/ 14 heterodimer (27E10 antigen) but not the single monomers [13].…”

Section: Antibodiesmentioning

confidence: 99%

“…To make sure that heterocomplexes between MRP8 and MRP14 are determined, a monoclonal antibody 27E10 was used as a captive antibody. The epitope of this antibody is generated by complex formation of both MRPs [13]. Maxi-Sorb Immunoplates (96-wel1, Nunc, Wiesbaden, Germany) were coated with affinity chromatography-purified monoclonal antibodies specific either for recombinant MRP8 or for recombinant MRP14, or specific for the heterocomplex of MRP8 and MRP14 in carbonate buffer, pH 9.5, overnight at 4°C or for 1 h at 37°C.…”

Section: Elisas Of Mrp8 Mrp14 and Mrp8/14mentioning

confidence: 99%

“…They are postulated to have intracellular functions either in control of the cell cycle, transduction of the Ca2+ signal, or inhibition of specific phosphorylation events [ 10,l I]. MRPS and MRP14 associate to heterocomplexes of various molecular ratios and are able to form a new epitope defined by the monoclonal antibody 27E 10 [12,13]. Elevated plasma levels of these two Ca2+ binding proteins can be found in different kinds of inflammatory diseases, such as cystic fibrosis [ 10,141, chronic bronchitis [ 151 and Crohn's disease [N.…”

Section: Introductionmentioning

confidence: 99%

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The myeloic related protein MRP8/14 (27E10 antigen)— usefulness as a potential marker for disease activity in ulcerative colitis and putative biological function

Lügering

Stoll

Schmid

et al. 1995

Eur J Clin Investigation

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Abstract. MRP8, MRP14 and their heterodimer MRP8/14 (27E10 antigen) are myeloic related proteins which have been shown to have a major role in inflammatory and immunological responses. In the present study monospecific antibodies against MRPs were used to investigate immunohistochemically the distribution of these proteins in routinely processed bowel tissues from 23 patients with ulcerative colitis (UC). MRP8, MRP14 and their heterocomplex MRP8/l4 were demonstrated in the majority of granulocytes and macrophages in tissues of patients with active UC. Furthermore by employing the ELISA technique we measured MRP8/14 serum levels in 62 patients with UC and the results were compared with those for healthy controls. Disease activities were determined by established clinical activity indices. Serum MRP8/14 concentrations were significantly ( P < 0.0001) increased in patients with active ulcerative colitis. No enhancement of serum levels were found for MRP14 and MRP8 alone, respectively. The follow-up of individual patients with initially active disease showed a decrease of MRP8/14 serum levels in parallel with clinical improvement following the start of therapy. It is thus concluded that MRP8/14 accurately reflects the degree of disease activity in UC. Further, possible biological function of MRPs seems to be associated with the heterodimeric form (27E10 antigen) rather than with individual proteins. Our morphological results confirm the finding of enhanced MRP8/14 serum levels in patients with active UC.

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Section: Antibodiesmentioning

confidence: 99%

Section: Elisas Of Mrp8 Mrp14 and Mrp8/14mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The myeloic related protein MRP8/14 (27E10 antigen)— usefulness as a potential marker for disease activity in ulcerative colitis and putative biological function

Lügering

Stoll

Schmid

et al. 1995

Eur J Clin Investigation

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“…S100A8/A9 are not expressed by tissue Mac (17,18) whereas Mac in inflammatory lesions may do so (19 -22) and, although not always coordinately expressed (21,22), S100A8/9 ϩve Mac produce high amounts of TNF and IL-1, suggesting a particular proinflammatory phenotype (23).…”

mentioning

confidence: 99%

IFN-γ and TNF Regulate Macrophage Expression of the Chemotactic S100 Protein S100A8

Geczy

2000

The Journal of Immunology

118

111

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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-γ, and TNF were distinct from the C-C chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage-inflammatory protein-1α (MIP-1α), 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-1α 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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“…These complexes translocate from cytoplasm to membranes, as well as to intermediate filaments, after elevation of intracellular Ca 2ϩ levels, and this correlates with the induction of inflammatory actions of granulocytes and monocytes. Thus, MRP8 and MRP14 seem to be important regulators of cytoskeletal/membrane interactions during phagocyte activation (17-19).The calcium-induced change in the complex pattern of these two proteins has been considered to be important for their biological function (15,19). For example, only the complex of MRP8 and MRP14 has been described to inhibit casein kinases I and II, two enzymes involved in regulation of gene expression via mediation of RNA polymerase activity (20).…”

mentioning

confidence: 99%

S100A12 Is Expressed Exclusively by Granulocytes and Acts Independently from MRP8 and MRP14

Vogl¹,

Pröpper²,

Hartmann³

et al. 1999

Journal of Biological Chemistry

Self Cite

195

157

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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.Granulocytes and monocytes are major effector cells during inflammatory processes. Undue activation of these cells is a pathophysiological factor in many diseases, e.g. rheumatoid arthritis and chronic inflammatory bowel disease (1-4). In monocytes and granulocytes, intracellular Ca 2ϩ regulates various acute response activities, such as respiratory burst, phagocytosis, degranulation, and release of degrading enzymes (5-8). One molecular pathway of calcium signal transduction is calcium-binding proteins of the S100 multigene family, which comprises a group of small, acidic proteins with a tissue-and cell cycle-specific expression (9 -11). S100 proteins contain two calcium-binding sites per molecule (12). Two members of this family have been found in human granulocytes and monocytes, called macrophage migration inhibitory factor-related protein 8 (MRP8) 1 (S100A8) and MRP14 (S100A9), which represent up to 40% of the calcium binding capacity in monocytes (13,14). Both proteins form noncovalently associated complexes in a calciumdependent manner (15, 16). These complexes translocate from cytoplasm to membranes, as well as to intermediate filaments, after elevation of intracellular Ca 2ϩ levels, and this correlates with the induction of inflammatory actions of granulocytes and monocytes. Thus, MRP8 and MRP14 seem to be important regulators of cytoskeletal/membrane interactions during phagocyte activation (17-19).The calcium-induced change in the complex pattern of these two proteins has been considered to be important for their biological function (15,19). For example, only the ...

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The calcium‐binding proteins MRP8 and MRP14 form a membrane‐associated heterodimer in a subset of monocytes/macrophages present in acute but absent in chronic inflammatory lesions

Cited by 186 publications

References 38 publications

The myeloic related protein MRP8/14 (27E10 antigen)— usefulness as a potential marker for disease activity in ulcerative colitis and putative biological function

The myeloic related protein MRP8/14 (27E10 antigen)— usefulness as a potential marker for disease activity in ulcerative colitis and putative biological function

IFN-γ and TNF Regulate Macrophage Expression of the Chemotactic S100 Protein S100A8

S100A12 Is Expressed Exclusively by Granulocytes and Acts Independently from MRP8 and MRP14

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