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S100a8  -  S100 calcium binding protein A8...

Mus musculus

Synonyms: 60B8Ag, AI323541, B8Ag, CFAg, CP-10, ...
 
 
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Disease relevance of S100a8

  • Results indicate that although the hinge region contributes significantly to the functional specificity of the S100 protein CP-10, sustained cellular recruitment typical of a delayed type hypersensitivity response is apparently dependent on the structural integrity of the protein [1].
  • Identification of the mouse calcium-binding proteins, MRP 8 and MRP 14, in Schistosoma mansoni-induced granulomas: biochemical and functional characterization [2].
  • Expression of the calcium-binding proteins MRP8 and MRP14 by early infiltrating cells in experimental contact dermatitis [3].
  • The expression of MRP8 and MRP14 in both forms of dermatitis correlated with the early influx of macrophages and with the cell density of the infiltrate [3].
  • In transplanted gliomas, CP-10+ cells are located exclusively within the tumor parenchyma [4].
  • Mrp8-Mrp14 complexes are new inflammatory components that amplify phagocyte activation during sepsis upstream of TNFalpha-dependent effects [5].
 

High impact information on S100a8

  • Myeloid-related protein 14 (MRP-14) and its heterodimeric partner, MRP-8, are cytosolic calcium-binding proteins, highly expressed in neutrophils and monocytes [6].
  • We found that CYP2E1 downregulation was significantly delayed in p8(-/-) liver compared with wild-type liver, allowing increased production of toxic CCl(4) derivatives [7].
  • The p8 protein is therefore an important element of hepatocyte stress response [7].
  • Serum alanine and aspartate aminotransferase activities were higher and peaked earlier in p8(-/-) mice than in wild-type mice, which is in agreement with the observation of significantly larger areas of necrosis in p8(-/-) liver [7].
  • The murine calcium binding protein S100A8 (A8) is a leukocyte chemoattractant, but high levels may be protective and scavenge hypochlorite [8].
 

Chemical compound and disease context of S100a8

 

Biological context of S100a8

  • We report here the cloning of mouse MRP8 and MRP14 and their pattern of expression during hematopoiesis [10].
  • We previously reported the purification and partial amino acid sequence of a novel murine cytokine designated CP-10, which has chemotactic activity for murine polymorphonuclear cells (PMN) and macrophages [1].
  • Purification and structural analysis of a murine chemotactic cytokine (CP-10) with sequence homology to S100 proteins [11].
  • Transient transfection of CP-10 cDNA into CV-1 cells confirmed the chemotactic activity of rCP-10 for murine PMN [1].
  • CP-10 appears to be the first protein of this family with a well defined function affecting cell migration, and its biological potency suggests an important role for this cytokine in cellular immune reactions [11].
 

Anatomical context of S100a8

  • The data indicate that MRP-14 and MRP-8 are dispensable for many myeloid cell functions [6].
  • Immunohistochemically, cells expressing MRP 8 and MRP 14 considerably increased in different murine tissues after Schistosoma mansoni infection and concentrated in liver around the dilated blood vessels and at the edge of granulomas [2].
  • Since the majority of S100 proteins exhibit their biological activity when associated as complex it was investigated whether murine MRP8 and MRP14 form heterodimers and whether this complex may bind lipids of the cell membrane [12].
  • 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 [13].
  • Mouse embryo fibroblasts (MEFs) from p8+/+ and p8-/- animals were transformed with the pBabe-rasV12/E1A retroviral vector, which expresses both the rasV12 mutated protein and the E1A oncogene [14].
 

Associations of S100a8 with chemical compounds

  • The 76-amino acid sequence, obtained by automated N-terminal microsequence analysis of native CP-10, and fragments derived from trypsin digestion and cyanogen bromide cleavage indicated no sequence identity with any known cytokine or chemotactic factor but revealed up to 55% sequence homology with S100, Ca2(+)-binding proteins [11].
  • The heterodimer of the Ca2+-binding proteins MRP8 and MRP14 binds to arachidonic acid [12].
  • KA-induced neurotoxic signs as shown by mortality and seizure activity were more accentuated in the SAM-P8 than in the SAM-R1 [15].
  • Immunodetection of the murine chemotactic protein CP-10 in bleomycin-induced pulmonary injury [16].
  • The analysis revealed that nasal antigen administration (without adiuvant) led to modulation of various proteins among which the most prominent were haptoglobin, nonintegrin 67 kDa laminin receptor, and MRP8 [17].
 

Other interactions of S100a8

  • Mouse MRP8 and MRP14, two intracellular calcium-binding proteins associated with the development of the myeloid lineage [10].
  • The resulting tryptic peptides were sequenced by tandem mass spectrometry, and based on the recovered partial amino acid sequences, three of the tumor specific protein markers were identified as calgranulin A (S100A8), calgranulin B (S100A9) and calgizzarin (S100A11) [18].
  • The murine S-100 protein designated CP-10 is a potent chemotactic factor for phagocytic cells, exhibiting optimal activity in the picomolar range [16].
 

Analytical, diagnostic and therapeutic context of S100a8

References

  1. Identification of a chemotactic domain of the pro-inflammatory S100 protein CP-10. Lackmann, M., Rajasekariah, P., Iismaa, S.E., Jones, G., Cornish, C.J., Hu, S., Simpson, R.J., Moritz, R.L., Geczy, C.L. J. Immunol. (1993) [Pubmed]
  2. Identification of the mouse calcium-binding proteins, MRP 8 and MRP 14, in Schistosoma mansoni-induced granulomas: biochemical and functional characterization. Yang, T.H., Tzeng, S., Cheng, I., Burnett, M.G., Yoshizawa, Y., Fukuyama, K., Lee, S.C., Epstein, W.L. J. Leukoc. Biol. (1997) [Pubmed]
  3. Expression of the calcium-binding proteins MRP8 and MRP14 by early infiltrating cells in experimental contact dermatitis. Roth, J., Sunderkötter, C., Goebeler, M., Gutwald, J., Sorg, C. Int. Arch. Allergy Immunol. (1992) [Pubmed]
  4. CP-10, a chemotactic peptide, is expressed in lesions of experimental autoimmune encephalomyelitis, neuritis, uveitis and in C6 gliomas. Deininger, M.H., Zhao, Y., Schluesener, H.J. J. Neuroimmunol. (1999) [Pubmed]
  5. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Vogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M.A., Nacken, W., Foell, D., van der Poll, T., Sorg, C., Roth, J. Nat. Med. (2007) [Pubmed]
  6. Myeloid cell function in MRP-14 (S100A9) null mice. Hobbs, J.A., May, R., Tanousis, K., McNeill, E., Mathies, M., Gebhardt, C., Henderson, R., Robinson, M.J., Hogg, N. Mol. Cell. Biol. (2003) [Pubmed]
  7. Inactivation of stress protein p8 increases murine carbon tetrachloride hepatotoxicity via preserved CYP2E1 activity. Taïeb, D., Malicet, C., Garcia, S., Rocchi, P., Arnaud, C., Dagorn, J.C., Iovanna, J.L., Vasseur, S. Hepatology (2005) [Pubmed]
  8. Il-10 up-regulates macrophage expression of the S100 protein S100A8. Xu, K., Yen, T., Geczy, C.L. J. Immunol. (2001) [Pubmed]
  9. Leishmanial amastigote antigen P-2 induces major histocompatibility complex class II-dependent natural killer-cell reactivity in cells from healthy donors. Nylén, S., Maasho, K., McMahon-Pratt, D., Akuffo, H. Scand. J. Immunol. (2004) [Pubmed]
  10. Mouse MRP8 and MRP14, two intracellular calcium-binding proteins associated with the development of the myeloid lineage. Lagasse, E., Weissman, I.L. Blood (1992) [Pubmed]
  11. Purification and structural analysis of a murine chemotactic cytokine (CP-10) with sequence homology to S100 proteins. Lackmann, M., Cornish, C.J., Simpson, R.J., Moritz, R.L., Geczy, C.L. J. Biol. Chem. (1992) [Pubmed]
  12. The heterodimer of the Ca2+-binding proteins MRP8 and MRP14 binds to arachidonic acid. Klempt, M., Melkonyan, H., Nacken, W., Wiesmann, D., Holtkemper, U., Sorg, C. FEBS Lett. (1997) [Pubmed]
  13. IFN-gamma and TNF regulate macrophage expression of the chemotactic S100 protein S100A8. Xu, K., Geczy, C.L. J. Immunol. (2000) [Pubmed]
  14. p8 is critical for tumour development induced by rasV12 mutated protein and E1A oncogene. Vasseur, S., Hoffmeister, A., Garcia, S., Bagnis, C., Dagorn, J.C., Iovanna, J.L. EMBO Rep. (2002) [Pubmed]
  15. Oxidative damage causes formation of lipofuscin-like substances in the hippocampus of the senescence-accelerated mouse after kainate treatment. Kim, H.C., Bing, G., Jhoo, W.K., Kim, W.K., Shin, E.J., Park, E.S., Choi, Y.S., Lee, D.W., Shin, C.Y., Ryu, J.R., Ko, K.H. Behav. Brain Res. (2002) [Pubmed]
  16. Immunodetection of the murine chemotactic protein CP-10 in bleomycin-induced pulmonary injury. Kumar, R.K., Harrison, C.A., Cornish, C.J., Kocher, M., Geczy, C.L. Pathology. (1998) [Pubmed]
  17. Antigens up the nose: identification of putative biomarkers for nasal tolerance induction functional studies combined with proteomics. Boots, A.M., Verhaert, P.D., te Poele, R.J., Evers, S., Coenen-de Roo, C.J., Cleven, J., Bos, E.S. J. Proteome Res. (2004) [Pubmed]
  18. Profiling proteins from azoxymethane-induced colon tumors at the molecular level by matrix-assisted laser desorption/ionization mass spectrometry. Chaurand, P., DaGue, B.B., Pearsall, R.S., Threadgill, D.W., Caprioli, R.M. Proteomics (2001) [Pubmed]
  19. Identification of noncovalent dimeric complexes of the recombinant murine S100 protein CP10 by electrospray ionization mass spectrometry and chemical cross-linking. Raftery, M.J., Geczy, C.L. J. Am. Soc. Mass Spectrom. (1998) [Pubmed]
  20. Display of functional alphabeta single-chain T-cell receptor molecules on the surface of bacteriophage. Weidanz, J.A., Card, K.F., Edwards, A., Perlstein, E., Wong, H.C. J. Immunol. Methods (1998) [Pubmed]
 
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