Protein Microarrays: Effective Tools for the Study of Inflammatory Diseases

  • Xiaobo Yu
  • Nicole Schneiderhan-Marra
  • Hsin-Yun Hsu
  • Jutta Bachmann
  • Thomas O. Joos
Protocol
Part of the Methods in Molecular Biology™ book series (MIMB, volume 577)

Summary

Inflammation is a defense reaction of an organism against harmful stimuli such as tissue injury or infectious agents. The relationship between the infecting microorganism and the immune, inflammatory, and coagulation responses of the host is intricately intertwined. Due to its complex nature, the molecular mechanisms of inflammation are not yet understood in detail and additional diagnostic tools are required to clarify further aspects. In recent years, protein microarray-based research has moved from being technology-based to application-oriented. Protein microarrays are perfect tools for studying inflammatory diseases. High-density protein arrays enable new classes of autoantibodies, which cause autoimmune diseases, to be discovered. Protein arrays consisting of miniaturized multiplexed sandwich immunoassays allow the simultaneous expression analysis of dozens of signaling molecules such as the cytokines and chemokines involved in the regulation of the immune system. The data enable statements to be made on the status of the disease and its progression as well as support for the clinicians in choosing patient-specific treatment. This chapter reviews the technology and the applications of protein microarrays in diagnosing and monitoring inflammatory diseases.

Key words

Protein microarray Inflammatory disease Multiple protein profiling Biomarker 

Notes

Acknowledgments

Dr. Xiaobo Yu’s research is supported by a Humboldt research fellowship (Alexander von Humboldt Foundation, Germany; fellowship ID: 1126997). Hsin-Yun Hsu is supported by the DAAD (German Academic Exchange Service), Germany (fellowship ID: A/04/07700).

References

  1. 1.
    Lissauer, M.E., et al. (2007) Coagulation and complement protein differences between septic and uninfected systemic inflammatory response syndrome patients. J Trauma. 62, 1082–92; discussion 1092–4.PubMedCrossRefGoogle Scholar
  2. 2.
    Tracey, K.J. (2002) The inflammatory reflex. Nature. 420, 853–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Carrigan, S.D., G. Scott, and M. Tabrizian (2004) Toward resolving the challenges of sepsis diagnosis. Clin Chem. 50, 1301–14.PubMedCrossRefGoogle Scholar
  4. 4.
    Hotchkiss, R.S. and D.W. Nicholson (2006) Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol. 6, 813–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Kemper, C. and J.P. Atkinson (2007) T-cell regulation: with complements from innate immunity. Nat Rev Immunol. 7, 9–18.PubMedCrossRefGoogle Scholar
  6. 6.
    Lin, W.W. and M. Karin (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest. 117, 1175–83.PubMedCrossRefGoogle Scholar
  7. 7.
    Purwar, R., et al. (2008) Modulation of keratinocyte-derived MMP-9 by IL-13: a possible role for the pathogenesis of epidermal inflammation. J Invest Dermatol. 128, 59–66.PubMedCrossRefGoogle Scholar
  8. 8.
    Stoll, D., et al. (2005) Protein microarrays: applications and future challenges. Curr Opin Drug Discov Devel. 8, 239–52.PubMedGoogle Scholar
  9. 9.
    Kricka, L.J., et al. (2006) Current perspectives in protein array technology. Ann Clin Biochem. 43, 457–67.PubMedCrossRefGoogle Scholar
  10. 10.
    Master, S.R., C. Bierl, and L.J. Kricka (2006) Diagnostic challenges for multiplexed protein microarrays. Drug Discov Today. 11, 1007–11.PubMedCrossRefGoogle Scholar
  11. 11.
    Chipping-Forecast-II (2002) Nature Genetics, 32(supplement), 461–552.Google Scholar
  12. 12.
    Stoll, D., et al. (2002) Protein microarray technology. Front Biosci. 7, c13–32.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu, Y., et al. (2007) Optimization of printing buffer for protein microarrays based on aldehyde-modified glass slides. Front Biosci. 12, 3768–73.PubMedCrossRefGoogle Scholar
  14. 14.
    Oh, S.J., et al. (2006) Surface modification for DNA and protein microarrays. OMICS. 10, 327–43.PubMedCrossRefGoogle Scholar
  15. 15.
    Matson, R.S., et al. (2007) Overprint immunoassay using protein A microarrays. Methods Mol Biol. 382, 273–86.PubMedCrossRefGoogle Scholar
  16. 16.
    Li, Y.J., et al. (2006) Reversible immobilization of proteins with streptavidin affinity tags on a surface plasmon resonance biosensor chip. Anal Bioanal Chem. 386, 1321–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Zhu, H., et al. (2001) Global analysis of protein activities using proteome chips. Science. 293, 2101–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Lauer, S.A. and J.P. Nolan (2002) Development and characterization of Ni-NTA-bearing microspheres. Cytometry. 48, 136–45.PubMedCrossRefGoogle Scholar
  19. 19.
    Waterboer, T., et al. (2005) Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin Chem. 51, 1845–53.PubMedCrossRefGoogle Scholar
  20. 20.
    Boozer, C., et al. (2006) DNA-directed protein immobilization for simultaneous detection of multiple analytes by surface plasmon resonance biosensor. Anal Chem. 78, 1515–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Lee, M., et al. (2006) Protein nanoarray on Prolinker surface constructed by atomic force microscopy dip-pen nanolithography for analysis of protein interaction. Proteomics. 6, 1094–103.PubMedCrossRefGoogle Scholar
  22. 22.
    Wang, Z., T. Wilkop, and Q. Cheng (2005), Characterization of micropatterned lipid membranes on a gold surface by surface plasmon resonance imaging and electrochemical signaling of a pore-forming protein. Langmuir. 21, 10292–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Rozkiewicz, D.I., et al. (2007) Dendrimer-mediated transfer printing of DNA and RNA microarrays. J Am Chem Soc. 129, 11593–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Mayer, M., et al. (2004) Micropatterned agarose gels for stamping arrays of proteins and gradients of proteins. Proteomics. 4, 2366–76.PubMedCrossRefGoogle Scholar
  25. 25.
    Palmer, R.E. and C. Leung (2007) Immobilisation of proteins by atomic clusters on surfaces. Trends Biotechnol. 25, 48–55.PubMedCrossRefGoogle Scholar
  26. 26.
    Barbulovic-Nad, I., et al. (2006) Bio-microarray fabrication techniques – a review. Crit Rev Biotechnol. 26, 237–59.PubMedCrossRefGoogle Scholar
  27. 27.
    Pawlak, M., et al. (2002) Zeptosens’ protein microarrays: a novel high performance microarray platform for low abundance protein analysis. Proteomics. 2, 383–93.PubMedCrossRefGoogle Scholar
  28. 28.
    Usui-Aoki, K., K. Shimada, and H. Koga (2007) A novel antibody microarray format using non-covalent antibody immobilization with chemiluminescent detection. Mol Biosyst. 3, 36–42.PubMedCrossRefGoogle Scholar
  29. 29.
    Guo, H., et al. (2005) Development of a low density colorimetric protein array for cardiac troponin I detection. J Nanosci Nanotechnol. 5, 2161–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Timlin, J.A. (2006) Scanning microarrays: current methods and future directions. Methods Enzymol. 411, 79–98.PubMedCrossRefGoogle Scholar
  31. 31.
    Yu, X., D. Xu, and Q. Cheng (2006) Label-free detection methods for protein microarrays. Proteomics. 6, 5493–503.PubMedCrossRefGoogle Scholar
  32. 32.
    Kingsmore, S.F. (2006) Multiplexed protein measurement: technologies and applications of protein and antibody arrays. Nat Rev Drug Discov. 5, 310–20.PubMedCrossRefGoogle Scholar
  33. 33.
    Templin, M.F., et al. (2002) Protein microarray technology. Trends Biotechnol. 20, 160–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Mendes, K.N., et al. (2007) Analysis of signaling pathways in 90 cancer cell lines by protein lysate array. J Proteome Res. 6, 2753–67.PubMedCrossRefGoogle Scholar
  35. 35.
    Sheehan, K.M., et al. (2008) Signal pathway profiling of epithelial and stromal compartments of colonic carcinoma reveals epithelial-mesenchymal transition. Oncogene. 27, 323–31.PubMedCrossRefGoogle Scholar
  36. 36.
    Geho, D.H., et al. (2007) Fluorescence-based analysis of cellular protein lysate arrays using quantum dots. Methods Mol Biol. 374, 229–37.PubMedGoogle Scholar
  37. 37.
    Templin, M.F., et al. (2004) Protein microarrays and multiplexed sandwich immunoassays: what beats the beads? Comb Chem High Throughput Screen. 7, 223–9.PubMedGoogle Scholar
  38. 38.
  39. 39.
    Singh, M. and L. Johnson (2006) Using genetically engineered mouse models of cancer to aid drug development: an industry perspective. Clin Cancer Res. 12, 5312–28.PubMedCrossRefGoogle Scholar
  40. 40.
    Toy, D., et al. (2006) Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol. 177, 36–9.PubMedGoogle Scholar
  41. 41.
    Perper, S.J., et al. (2006) TWEAK is a novel arthritogenic mediator. J Immunol. 177, 2610–20.PubMedGoogle Scholar
  42. 42.
    Fath, M.A., et al. (2005) Mkks-null mice have a phenotype resembling Bardet–sBiedl syndrome. Hum Mol Genet. 14, 1109–18.PubMedCrossRefGoogle Scholar
  43. 43.
    Heuer, J.G., et al. (2004) Evaluation of protein C and other biomarkers as predictors of mortality in a rat cecal ligation and puncture model of sepsis. Crit Care Med. 32, 1570–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Heuer, J.G., D.J. Cummins, and B.T. Edmonds (2005) Multiplex proteomic approaches to sepsis research: case studies employing new technologies. Expert Rev Proteomics. 2, 669–80.PubMedCrossRefGoogle Scholar
  45. 45.
    Hsu, H.Y., S. Wittemann, and T.O. Joos (2008) Miniaturized parallelized sandwich immunoassays. Methods Mol Biol. 428, 247–61.PubMedCrossRefGoogle Scholar
  46. 46.
    Kader, H.A., et al. (2005) Protein microarray analysis of disease activity in pediatric inflammatory bowel disease demonstrates elevated serum PLGF, IL-7, TGF-beta1, and IL-12p40 levels in Crohn’s disease and ulcerative colitis patients in remission versus active disease. Am J Gastroenterol. 100, 414–23.PubMedCrossRefGoogle Scholar
  47. 47.
    Decalf, J., et al. (2007) Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients. J Exp Med. 204, 2423–37.PubMedCrossRefGoogle Scholar
  48. 48.
    Tang, X., et al. (2005) LPS induces the interaction of a transcription factor, LPS-induced TNF-alpha factor, and STAT6(B) with effects on multiple cytokines. Proc Natl Acad Sci U S A. 102, 5132–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Datta, A., et al. (2006) The HTLV-I p30 interferes with TLR4 signaling and modulates the release of pro- and anti-inflammatory cytokines from human macrophages. J Biol Chem. 281, 23414–24.PubMedCrossRefGoogle Scholar
  50. 50.
    Andreas, K., et al. (2008) Key regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitro study. Arthritis Res Ther. 10, R9.PubMedCrossRefGoogle Scholar
  51. 51.
    Hueber, W., et al. (2005) Antigen microarray profiling of autoantibodies in rheumatoid arthritis. Arthritis Rheum. 52, 2645–55.PubMedCrossRefGoogle Scholar
  52. 52.
    Hudson, M.E., et al. (2007) Identification of differentially expressed proteins in ovarian cancer using high-density protein microarrays. Proc Natl Acad Sci USA. 104, 17494–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Celis, J.E., et al. (2004) Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment: a novel resource for biomarker and therapeutic target discovery. Mol Cell Proteomics. 3, 327–44.PubMedCrossRefGoogle Scholar
  54. 54.
    Kline, M., et al. (2007) Cytokine and chemokine profiles in multiple myeloma; significance of stromal interaction and correlation of IL-8 production with disease progression. Leuk Res. 31, 591–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Carson, R.T. and D.A. Vignali (1999) Simultaneous quantitation of 15 cytokines using a multiplexed flow cytometric assay. J Immunol Methods. 227, 41–52.PubMedCrossRefGoogle Scholar
  56. 56.
    Prabhakar, U., E. Eirikis, and H.M. Davis (2002) Simultaneous quantification of proinflammatory cytokines in human plasma using the LabMAP assay. J Immunol Methods. 260, 207–18.PubMedCrossRefGoogle Scholar
  57. 57.
    de Jager, W., et al. (2003) Simultaneous detection of 15 human cytokines in a single sample of stimulated peripheral blood mononuclear cells. Clin Diagn Lab Immunol. 10, 133–9.PubMedGoogle Scholar
  58. 58.
    Olsson, A., et al. (2005) Simultaneous measurement of beta-amyloid(1–42), total tau, and phosphorylated tau (Thr181) in cerebrospinal fluid by the xMAP technology. Clin Chem. 51, 336–45.PubMedCrossRefGoogle Scholar
  59. 59.
    de Jager, W. and G.T. Rijkers (2006) Solid-phase and bead-based cytokine immunoassay: a comparison. Methods. 38, 294–303.PubMedCrossRefGoogle Scholar
  60. 60.
    Maier, R., et al. (2006) Application of multiplex cytometric bead array technology for the measurement of angiogenic factors in the vitreous. Mol Vis. 12, 1143–7.PubMedGoogle Scholar
  61. 61.
    McDuffie, E., et al. (2006) Detection of cytokine protein expression in mouse lung homogenates using suspension bead array. J Inflamm (Lond). 3, 15.CrossRefGoogle Scholar
  62. 62.
    Kofoed, K., et al. (2007) Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care. 11, R38.PubMedCrossRefGoogle Scholar
  63. 63.
    Rossi, D. and A. Zlotnik (2000) The biology of chemokines and their receptors. Annu Rev Immunol. 18, 217–42.PubMedCrossRefGoogle Scholar
  64. 64.
    Zlotnik, A. and O. Yoshie (2000) Chemokines: a new classification system and their role in immunity. Immunity. 12, 121–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Bozza, F.A., et al. (2007) Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care. 11, R49.PubMedCrossRefGoogle Scholar
  66. 66.
    Calvano, S.E., et al. (1996) Monocyte tumor necrosis factor receptor levels as a predictor of risk in human sepsis. Arch Surg. 131, 434–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Pruitt, J.H., et al. (1996) Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome. Blood. 87, 3282–8.PubMedGoogle Scholar
  68. 68.
    Keh, D., et al. (2003) Immunologic and hemodynamic effects of “low-dose” hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med. 167, 512–20.PubMedCrossRefGoogle Scholar
  69. 69.
    Hsu, H.Y., et al. (2008) Suspension microarrays for the identification of the response patterns in hyperinflammatory diseases. Med Eng Phys 30, 976–83.PubMedCrossRefGoogle Scholar
  70. 70.
    Kofoed, K., et al. (2006) Development and validation of a multiplex add-on assay for sepsis biomarkers using xMAP technology. Clin Chem. 52, 1284–93.PubMedCrossRefGoogle Scholar
  71. 71.
    Lin, Y., et al. (2002) Profiling of human cytokines in healthy individuals with vitamin E supplementation by antibody array. Cancer Lett. 187, 17–24.PubMedCrossRefGoogle Scholar
  72. 72.
    Zhang, J.Z. and K.W. Ward (2008) Besifloxacin, a novel fluoroquinolone antimicrobial agent, exhibits potent inhibition of pro-inflammatory cytokines in human THP-1 monocytes. J Antimicrob Chemother. 61, 111–6.PubMedCrossRefGoogle Scholar
  73. 73.
    Joos, T.O. and H. Berger (2006) The long and difficult road to the diagnostic market: protein microarrays. Drug Discov Today. 11, 959–61.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Xiaobo Yu
    • 1
  • Nicole Schneiderhan-Marra
    • 1
  • Hsin-Yun Hsu
    • 1
  • Jutta Bachmann
    • 2
  • Thomas O. Joos
    • 1
  1. 1.NMI Natural and Medical Sciences Institute at the University of TübingenReutlingenGermany
  2. 2.Bachmann ConsultingNesoddtangenNorway

Personalised recommendations