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The Lymph Proteome, Peptidome, and Degradome

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Immunology of the Lymphatic System

Abstract

During the last decade advanced proteomic analysis have allowed detailed characterization of the composition of the lymphatic fluid. A picture start to emerge indicating that far from being an ultra filtrate of the plasma the lymph carries a rich repertoire of proteins and peptides reflecting the tissue of origin and its physiological state. Indeed in few pathological conditions it has been shown that proteins transported by the lymph closely represent a molecular signature of the diseased organs. Altogether the “omic analysis” (proteomic, peptidomic, degradomic and lipidomic) prove to be a powerful tool to fingerprint variations in the lymph fluid collected from different parenchymal organs and to discover molecular biomarkers for the early detection of diseases.

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References

  • Ahn S-M, Simpson RJ (2007) Body fluid proteomics: prospects for biomarker discovery. Proteomics Clin Appl 1(9):1004–1015

    Article  PubMed  CAS  Google Scholar 

  • Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, Veenstra TD, Adkins JN, Pounds JG, Fagan R, Lobley A (2004) The human plasma proteome: a nonredundant list developed by combination of four separate sources. Mol Cell Proteomics 3:311–326

    Article  PubMed  CAS  Google Scholar 

  • Antwi K, Hostetter G, Demeure MJ, Katchman BA, Decker GA, Ruiz Y, Sielaff TD, Koep LJ, Lake DF (2009) Analysis of the plasma peptidome from pancreas cancer patients connects a peptide in plasma to overexpression of the parent protein in tumors. J Proteome Res 8(10):4722–4731

    Article  PubMed  CAS  Google Scholar 

  • Armandola EA (2003) Proteome profiling in body fluids and in cancer cell signaling. MedGenMed 5(2):18

    PubMed  Google Scholar 

  • Brewis IA, Brennan P (2010) Proteomics technologies for the global identification and quantification of proteins. Adv Protein Chem Struct Biol 80:1–44

    Article  PubMed  CAS  Google Scholar 

  • Carvalho PC, Fischer JS, Chen EI, Domont GB, Carvalho MG, Degrave WM, Yates JR III, Barbosa VC (2009) GO Explorer: a gene-ontology tool to aid in the interpretation of shotgun proteomics data. Proteome Sci 7:6

    Article  PubMed  Google Scholar 

  • Chen EI, Yates JR III (2007) Cancer proteomics by quantitative shotgun proteomics. Mol Oncol 1(2):144–159

    Article  PubMed  Google Scholar 

  • Chen EI, Hewel J, Felding-Habermann B, Yates JR III (2006) Large scale protein profiling by combination of protein fractionation and multidimensional protein identification technology (MudPIT). Mol Cell Proteomics 5(1):53–56

    PubMed  CAS  Google Scholar 

  • Clement CC, Cannizzo ES, Nastke MD, Sahu R, Olszewski W, Miller NE, Stern LJ, Santambrogio L (2010) An expanded self-antigen peptidome is carried by the human lymph as compared to the plasma. PLoS One 5(3):e9863

    Article  PubMed  Google Scholar 

  • Clement CC, Rotzschke O, Santambrogio L (2011) The lymph as a pool of self-antigens. Trends Immunol 32(1):6–11

    Article  PubMed  CAS  Google Scholar 

  • Clement CC, Aphkhazava D, Nieves E, Callaway M, Olszewsky W, Rotzschke O, Santambrogio L (2013) Protein expression profiles of human lymph and plasma mapped by 2D-Dige and 1D SDSpage coupled with nanolc-ESI-MS/MS bottom up proteomics. J Proteomics 78:172–187

    Article  Google Scholar 

  • Dzieciatkowska M, Wohlauer MV, Moore EE, Damle S, Peltz E, Campsen J, Kelher M, Silliman C, Banerjee A, Hansen KC (2011) Proteomic analysis of human mesenteric lymph. Shock 35(4):331–338

    Article  PubMed  Google Scholar 

  • Echan LA, Tang HY, Li-Khan N, Lee K, Speicher DW (2005) Depletion of multiple high-­abundance proteins improves protein profiling capacities of human serum and plasma. Proteomics 13:3292–3303

    Article  Google Scholar 

  • Fang JF, Shih LY, Yuan KC, Fang KY, Hwang TL, Hsieh SY (2010) Proteomic analysis of post-­hemorrhagic shock mesenteric lymph. Shock 34(3):291–298

    Article  PubMed  CAS  Google Scholar 

  • Farrah T, Deutsch EW, Omenn GS, Campbell DS, Sun Z, Bletz JA, Mallick P, Katz JE, Malmstrom J, Ossola R, Watts JD, Lin B, Zhang H, Moritz RL, Aebersold RH (2011) A high confidence human plasma proteome reference set with estimated concentrations in PeptideAtlas. Mol Cell Proteomics 10(9):M110.006353

    Article  PubMed  Google Scholar 

  • Geho DH, Liotta LA, Petricoin EF, Zhao W, Araujo RP (2006) The amplified peptidome: the new treasure chest of candidate biomarkers. Curr Opin Chem Biol 10(1):50–55

    Article  PubMed  CAS  Google Scholar 

  • Goldfinch GM, Smith WD, Imrie L, McLean K, Inglis NF, Pemberton AD (2008) The proteome of gastric lymph in normal and nematode infected sheep. Proteomics 8(9):1909–1918

    Article  PubMed  CAS  Google Scholar 

  • Gretz JE, Kaldjian EP, Anderson AO, Shaw S (1996) Sophisticated strategies for information encounter in the lymph node: the reticular network as a conduit of soluble information and a highway for cell traffic. J Immunol 157:495–499

    PubMed  CAS  Google Scholar 

  • Han X, Aslanian A, Yates JR III (2008) Mass spectrometry for proteomics. Curr Opin Chem Biol 12(5):483–490

    Article  PubMed  CAS  Google Scholar 

  • Hood BL, Lucas DA, Kim G, Chan KC, Blonder J, Issaq HJ, Veenstra TD, Conrads TP, Pollet I, Karsan A (2005) Quantitative analysis of the low molecular weight serum proteome using 18O stable isotope labeling in a lung tumor xenograft mouse model. J Am Soc Mass Spectrom 16(8):1221–1230

    Article  PubMed  CAS  Google Scholar 

  • Interewicz B, Olszewski WL, Leak LV, Petricoin EF, Liotta LA (2004) Profiling of normal human leg lymph proteins using the 2-D electrophoresis and SELDI-TOF mass spectrophotometry approach. Lymphology 37:65–72

    PubMed  CAS  Google Scholar 

  • Jiao X, Sherman BT, Stephens R, Baseler MW, Lane HC, Lempicki RA (2012) DAVID-WS: a stateful web service to facilitate gene/protein list analysis. Bioinformatics 28(13):1805–1806

    Article  PubMed  CAS  Google Scholar 

  • Jimenez CR, Piersma S, Pham TV (2007) High-throughput and targeted in-depth mass spectrometry-­based approaches for biofluid profiling and biomarker discovery. Biomark Med 1(4):541–565

    Article  PubMed  CAS  Google Scholar 

  • Jordan JR, Moore EE, Damle SS, Eckels P, Johnson JL, Roach JP, Redzic JS, Hansen KC, Banerjee A (2007) Gelsolin is depleted in post-shock mesenteric lymph. J Surg Res 143(1):130–135

    Article  PubMed  CAS  Google Scholar 

  • Kawashima Y, Fukutomi T, Tomonaga T, Takahashi H, Nomura F, Maeda T, Kodera Y (2010) High-yield peptide-extraction method for the discovery of subnanomolar biomarkers from small serum samples. J Proteome Res 9(4):1694–1705

    Article  PubMed  CAS  Google Scholar 

  • Koomen JM, Li D, Xiao LC, Liu TC, Coombes KR, Abbruzzese J, Kobayashi R (2005) Direct tandem mass spectrometry reveals limitations in protein profiling experiments for plasma biomarker discovery. J Proteome Res 4(3):972–981

    Article  PubMed  CAS  Google Scholar 

  • Leak LV, Liotta LA, Krutzsch H, Jones M, Fusaro VS, Ross SJ, Zhao Y, Petricoin EF III (2004) Proteomic analysis of lymph. Proteomics 4:753–765

    Article  PubMed  CAS  Google Scholar 

  • Lin D, Tabb DL, Yates JR III (2003) Large-scale protein identification using mass spectrometry. Biochim Biophys Acta 1646(1–2):1–10

    PubMed  CAS  Google Scholar 

  • Masuno T, Moore EE, Cheng AM, Sarin EL, Banerjee A (2006) Bioactivity of postshock mesenteric lymph depends on the depth and duration of hemorrhagic shock. Shock 26(3):285–289

    Article  PubMed  Google Scholar 

  • Meng Z, Veenstra TD (2007) Proteomic analysis of serum, plasma, and lymph for the identification of biomarkers. Proteomics Clin Appl 1(8):747–757

    Article  PubMed  CAS  Google Scholar 

  • Meng Z, Veenstra TD (2011) Targeted mass spectrometry approaches for protein biomarker verification. J Proteomics 74(12):2650–2659

    Article  PubMed  CAS  Google Scholar 

  • Mittal A, Middleditch M, Ruggiero K, Buchanan CM, Jullig M, Loveday B, Cooper GJ, Windsor JA, Phillips AR (2008) The proteome of rodent mesenteric lymph. Am J Physiol Gastrointest Liver Physiol 295(5):G895–G903

    Article  PubMed  CAS  Google Scholar 

  • Mittal A, Phillips AR, Middleditch M, Ruggiero K, Loveday B, Delahunt B, Cooper GJ, Windsor JA (2009) The proteome of mesenteric lymph during acute pancreatitis and implications for treatment. JOP 10(2):130–142

    PubMed  Google Scholar 

  • Motoyama A, Yates JR III (2008) Multidimensional LC separations in shotgun proteomics. Anal Chem 80(19):7187–7193

    Article  PubMed  CAS  Google Scholar 

  • Nanjee MN, Cooke CJ, Olszewski WL, Miller NL (2000) Lipid and apolipoprotein concentrations in prenodal leg lymph of fasted humans. Associations with plasma concentrations in normal subjects, lipoprotein lipase deficiency, and LCAT deficiency. J Lipid Res 41:1317–1327

    PubMed  CAS  Google Scholar 

  • Olszewski WL (1991) Lymph stasis: pathophysiology, diagnosis and treatment. CRC, Boca Raton, FL, pp 235–280 (Chaps. 10–11)

    Google Scholar 

  • Olszewski WL, Pazdur J, Kubasiewicz E, Zaleska M, Cooke CJ, Miller NE (2001) Lymph draining from foot joints in rheumatoid arthritis provides insight into local cytokine and chemokine production and transport to lymph nodes. Arthritis Rheum 44:541–549

    Article  PubMed  CAS  Google Scholar 

  • Omenn GS, States DJ, Adamski M, Blackwell TW, Menon R, Hermjakob H, Apweiler R, Haab BB, Simpson RJ, Eddes JS, Kapp EA, Moritz RL, Chan DW, Rai AJ, Admon A, Aebersold R, Eng J, Hancock WS, Hefta SA, Meyer H, Paik YK, Yoo JS, Ping P, Pounds J, Adkins J, Qian X, Wang R, Wasinger V, Wu CY, Zhao X, Zeng R, Archakov A, Tsugita A, Beer I, Pandey A, Pisano M, Andrews P, Tammen H, Speicher DW, Hanash SM (2005) Overview of the HUPO Plasma Proteome Project: Results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database. Proteomics 13:3226–3245

    Article  Google Scholar 

  • Peltz ED, Moore EE, Zurawel AA, Jordan JR, Damle SS, Redzic JS, Masuno T, Eun J, Hansen KC, Banerjee A (2009) Proteome and system ontology of hemorrhagic shock: exploring early constitutive changes in postshock mesenteric lymph. Surgery 146(2):347–357

    Article  PubMed  Google Scholar 

  • Pham TV, Piersma SR, Oudgenoeg G, Jimenez CR (2012) Label-free mass spectrometry-based proteomics for biomarker discovery and validation. Expert Rev Mol Diagn 12(4):343–359

    Article  PubMed  CAS  Google Scholar 

  • Qian WJ, Jacobs JM, Liu T, Camp DG II, Smith RD (2006) Advances and challenges in liquid chromatography-mass spectrometry-based proteomics profiling for clinical applications. Mol Cell Proteomics 5(10):1727–1744

    Article  PubMed  CAS  Google Scholar 

  • Shen Z, Want EJ, Chen W, Keating W, Nussbaumer W, Moore R, Gentle TM, Siuzdak G (2006) Sepsis plasma protein profiling with immunodepletion, three-dimensional liquid chromatography tandem mass spectrometry, and spectrum counting. J Proteome Res 5:3154–3160

    Article  PubMed  CAS  Google Scholar 

  • Shen Y, Liu T, Tolić N, Petritis BO, Zhao R, Moore RJ, Purvine SO, Camp DG, Smith RD (2010a) Strategy for degradomic-peptidomic analysis of human blood plasma. J Proteome Res 9(5):2339–2346

    Article  PubMed  CAS  Google Scholar 

  • Shen Y, Tolić N, Liu T, Zhao R, Petritis BO, Gritsenko MA, Camp DG, Moore RJ, Purvine SO, Esteva FJ, Smith RD (2010b) Blood peptidome-degradome profile of breast cancer. PLoS One 5(10):e13133

    Article  PubMed  Google Scholar 

  • Shen Y, Tolić N, Xie F, Zhao R, Purvine SO, Schepmoes AA, Moore RJ, Anderson GA, Smith RD (2011) Effectiveness of CID, HCD, and ETD with FT MS/MS for degradomic-peptidomic analysis: comparison of peptide identification methods. J Proteome Res 10(9):3929–3943

    Article  PubMed  CAS  Google Scholar 

  • Shen Y, Tolić N, Purvine SO, Smith RD (2012) Improving collision induced dissociation (CID), high energy collision dissociation (HCD), and electron transfer dissociation (ETD) Fourier transform MS/MS degradome-peptidome identifications using high accuracy mass information. J Proteome Res 11(2):668–677

    Article  PubMed  CAS  Google Scholar 

  • Tannu NS, Hemby SE (2006) Two-dimensional fluorescence difference gel electrophoresis for comparative proteomics profiling. Nat Protoc 1:1732–1742

    Article  PubMed  CAS  Google Scholar 

  • Veenstra TD, Conrads TP, Hood BL, Avellino AM, Ellenbogen RG, Morrison RS (2005) Biomarkers: mining the biofluid proteome. Mol Cell Proteomics 4(4):409–418

    Article  PubMed  CAS  Google Scholar 

  • Völkel P, Le Faou P, Angrand PO (2010) Interaction proteomics: characterization of protein complexes using tandem affinity purification-mass spectrometry. Biochem Soc Trans 38(4):883–887

    Article  PubMed  Google Scholar 

  • Whiteaker JR, Zhang H, Eng JK, Fang R, Piening BD, Feng LC, Lorentzen TD, Schoenherr RM, Keane JF, Holzman T, Fitzgibbon M, Lin C, Zhang H, Cooke K, Liu T, Camp DG II, Anderson L, Watts J, Smith RD, McIntosh MW, Paulovich AG (2007) Head-to-head comparison of serum fractionation techniques. J Proteome Res 6:828–836

    Article  PubMed  CAS  Google Scholar 

  • Yang W, Steen H, Freeman MR (2008) Proteomic approaches to the analysis of multiprotein signaling complexes. Proteomics 8(4):832–851

    Article  PubMed  CAS  Google Scholar 

  • Zheng X, Wu SL, Hincapie M, Hancock WS (2009) Study of the human plasma proteome of rheumatoid arthritis. J Chromatogr A 1216(16):3538–3545

    Article  PubMed  CAS  Google Scholar 

  • Zhou M, Lucas DA, Chan KC, Issaq HJ, Petricoin E III, Liotta LA, Veenstra TD, Conrads TP (2004) An investigation into the human serum “interactome”. Electrophoresis 25(9):1289–1298

    Article  PubMed  CAS  Google Scholar 

  • Ziganshin R, Arapidi G, Azarkin I, Zaryadieva E, Alexeev D, Govorun V, Ivanov V (2011) New method for peptide desorption from abundant blood proteins for plasma/serum peptidome analyses by mass spectrometry. J Proteomics 74(5):595–606

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman LJ, Li M, Yarbrough WG, Slebos RJ, Liebler DC (2012) Global stability of plasma proteomes for mass spectrometry-based analyses. Mol Cell Proteomics 11(6):M111.014340

    Article  PubMed  Google Scholar 

  • Zou X, Zhong L, Liu D, Yang B, Lou Y, Peng J, Rainer M, Feuerstein I, Muhammad NU, Huck CW, Bonn GK, Yin Y (2011) Novel multifunctional chitosan-GMA-IDA-Cu(II) nanospheres for high dynamic range characterization of the human plasma proteome. Anal Bioanal Chem 400(3):747–756

    Article  PubMed  CAS  Google Scholar 

  • Zurawel A, Moore EE, Peltz ED, Jordan JR, Da mle S, Dzieciatkowska M, Banerjee A, Hansen KC (2010) Proteomic profiling of the mesenteric lymph after hemorrhagic shock: differential gel electrophoresis and mass spectrometry analysis. Clin Proteomics 8(1):1

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY, USA

    Cristina C. Clement & Laura Santambrogio

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  1. Cristina C. Clement
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  2. Laura Santambrogio
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Correspondence to Cristina C. Clement .

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  1. 1300 Morris Park Avenue, Bronx, 10461, New York, USA

    Laura Santambrogio

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Clement, C.C., Santambrogio, L. (2013). The Lymph Proteome, Peptidome, and Degradome. In: Santambrogio, L. (eds) Immunology of the Lymphatic System. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3235-7_5

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