Abstract
Low-molecular–weight cellular signalling mediators orchestrate a programmed progression of a series of biological phenomena, including inflammation. In order to understand the biochemical basis of inflammatory diseases, it is important to first understand the spatiotemporal dynamics (i.e., production, diffusion, decomposition) of such inflammatory mediators in tissues; however, the lack of effective molecular imaging technology has made it difficult to determine their localisations in vivo. Because the in vivo concentrations of these mediators are maintained at low levels due to their strong ability to induce an inflammatory response, technological breakthroughs in molecular imaging methods toward a highly sensitive technology sufficient to detect inflammatory mediators in tissues are required.
We and other groups have attempted to fill this technical gap by developing highly sensitive imaging mass spectrometry (IMS) technologies. Owing to recent improvements in IMS regarding its sensitivity, molecular coverage, and spatial resolution, this imaging technology is expected to be a powerful and practical tool to reveal unexpected dynamics of inflammatory mediators in the tissues involved in chronic inflammation. Here, we review recent progress in the development of this technology and demonstrate how the highly sensitive IMS technique has contributed to increasing our general understanding of the biological basis of disease mechanisms.
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Abbreviations
- ESI:
-
electrospray ionisation
- FMW:
-
head-focused microwave irradiation
- IMS:
-
imaging mass spectrometry
- ISF:
-
in situ freezing
- MALDI:
-
matrix-assisted laser desorption/ionisation
References
Bai ZB, Cai LJ, Umemoto E, Takeda A, Tohya K, Komai Y, Veeraveedu PT, Hata E, Sugiura Y, Kubo A, Suematsu M, Hayasaka H, Okudaira S, Aoki J, Tanaka T, Albers HMHG, Ovaa H, Miyasaka M (2013) Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis. J Immunol 190:2036–2048
Bao Y, Mukai K, Hishiki T, Kubo A, Ohmura M, Sugiura Y, Matsuura T, Nagahata Y, Hayakawa N, Yamamoto T, Fukuda R, Saya H, Suematsu M, Minamishima YA (2013) Energy management by enhanced glycolysis in G(1)-phase in human colon cancer cells in vitro and in vivo. Mol Cancer Res 11:973–985
Beck G, Sugiura Y, Shinzawa K, Kato S, Setou M, Tsujimoto Y, Sakoda S, Sumi-Akamaru H (2011) Neuroaxonal dystrophy in calcium-independent phospholipase A(2)beta deficiency results from insufficient remodeling and degeneration of mitochondrial and presynaptic membranes. J Neurosci 31:11411–11420
Blatherwick EQ, Svensson CI, Frenguelli BG, Scrivens JH (2013) Localisation of adenine nucleotides in heat-stabilised mouse brains using ion mobility enabled MALDI imaging. Int J Mass Spectrom 345:19–27
Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, Lin ME, Teo ST, Park KE, Mosley AN, Chun J (2010) LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol 50:157–186
Cima G (2013) AVMA guidelines for the euthanasia of animal, edition. Javma-J Am Vet Med A 242:715–716
Cornett DS, Reyzer ML, Chaurand P, Caprioli RM (2007) MALDI imaging mass spectrometry: molecular snapshots of biochemical systems. Nat Methods 4:828–833
Cornett DS, Frappier SL, Caprioli RM (2008) MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue. Anal Chem 80:5648–5653
Debois D, Bralet MP, Le Naour F, Brunelle A, Laprevote O (2009) In Situ lipidomic analysis of nonalcoholic fatty liver by cluster TOF-SIMS imaging. Anal Chem 81:2823–2831
Delaney SM, Geiger JD (1996) Brain regional levels of adenosine and adenosine nucleotides in rats killed by high-energy focused microwave irradiation. J Neurosci Methods 64:151–156
Fletcher JS, Lockyer NP, Vaidyanathan S, Vickerman JC (2007) TOF-SIMS 3D biomolecular imaging of Xenopus laevis oocytes using buckminsterfullerene (C-60) primary ions. Anal Chem 79:2199–2206
Franck J, Arafah K, Elayed M, Bonnel D, Vergara D, Jacquet A, Vinatier D, Wisztorski M, Day R, Fournier I, Salzet M (2009) MALDI imaging mass spectrometry: state of the art technology in clinical proteomics. Mol Cell Proteomics 8:2023–2033
Girod M, Shi Y, Cheng JX, Cooks RG (2011) Mapping lipid alterations in traumatically injured rat spinal cord by desorption electrospray ionization imaging mass spectrometry. Anal Chem 83:207–215
Hanada M, Sugiura Y, Shinjo R, Masaki N, Imagama S, Ishiguro N, Matsuyama Y, Setou M (2012) Spatiotemporal alteration of phospholipids and prostaglandins in a rat model of spinal cord injury. Anal Bioanal Chem 403:1873–1884
Hata E, Sasaki1 N, Takeda A, Tohya K, Umemoto E, Akahoshi N, Ishii S, Bando K, Abe T, Kano K, Aoki J, H. Hayasaka H, Miyasaka M (2016) Lysophosphatidic acid receptors LPA4 and LPA6 differentially promote lymphocyte transmigration across high endothelial venules in lymph nodes. Int Immunol 28:283–292
Hattori K, Kajimura M, Hishiki T, Nakanishi T, Kubo A, Nagahata Y, Ohmura M, Yachie-Kinoshita A, Matsuura T, Morikawa T, Nakamura T, Setou M, Suematsu M (2010) Paradoxical ATP elevation in ischemic penumbra revealed by quantitative imaging mass spectrometry. Antioxid Redox Signal 13:1157–1167
Ifa DR, Wiseman JM, Song QY, Cooks RG (2007) Development of capabilities for imaging mass spectrometry under ambient conditions with desorption electrospray ionization (DESI). Int J Mass Spectrom 259:8–15
Ishii S, Noguchi K, Yanagida K (2009) Non-Edg family lysophosphatidic acid (LPA) receptors. Prostaglandins Other Lipid Mediat 89:57–65
Kerr SE (1935) Studies on the phosphorus compounds of brain. I. Phosphocreatine. J Biol Chem 110:625–635
Kim TW, Cho HM, Choi SY, Suguira Y, Hayasaka T, Setou M, Koh HC, Hwang EM, Park JY, Kang SJ, Kim HS, Kim H, Sun W (2013) (ADP-ribose) polymerase 1 and AMP-activated protein kinase mediate progressive dopaminergic neuronal degeneration in a mouse model of Parkinson’s disease. Cell Death Dis 4:e919. doi:10.1038/cddis.2013.447
Kinnersley HW, Peters RA (1929) Observations upon carbohydrate metabolism in birds. I. The relation between the lactic acid content of the brain and the symptoms of opisthotonus in rice-fed pigeons. Biochem J 23:1126–1136
Kunisawa J, Sugiura Y, Wake T, Nagatake T, Suzuki H, Nagasawa R, Shikata S, Honda K, Hashimoto E, Suzuki Y, Setou M, Suematsu M, Kiyono H (2015) Mode of bioenergetic metabolism during B cell differentiation in the intestine determines the distinct requirement for Vitamin B1. Cell Rep 13:122–131
Lawrence T, Willoughby DA, Gilroy DW (2002) Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat Rev Immunol 2:787–795
Luster AD, Tager AM (2004) T-cell trafficking in asthma: lipid mediators grease the way. Nat Rev Immunol 4:711–724
Marshall AG, Hendrickson CL, Jackson GS (1998) Fourier transform ion cyclotron resonance mass spectrometry: a primer. Mass Spectrom Rev 17:1–35
Maruyama Y, Iida N, Horikawa A, Hosoya E (1978) A new microwave device for rapid thermal fixation of the murine brain. J Microw Power 13:53–57
Matsumoto J, Sugiura Y, Yuki D, Hayasaka T, Goto-Inoue N, Zaima N, Kunii Y, Wada A, Yang Q, Nishiura K, Akatsu H, Hori A, Hashizume Y, Yamamoto T, Ikemoto K, Setou M, Niwa S (2011) Abnormal phospholipids distribution in the prefrontal cortex from a patient with schizophrenia revealed by matrix-assisted laser desorption/ionization imaging mass spectrometry. Anal Bioanal Chem 400:1933–1943
McGinty DA, Gesell R (1925) On the chemical regulation of respiration. II. A quantitative study of the accumulation of lactic acid in the isolated brain during anaerobic conditions and the role of lactic acid as a continuous regulator of respiration. Am J Physiol 75:70–83
Moree WJ, Phelan VV, Wu CH, Bandeira N, Cornett DS, Duggan BM, Dorrestein PC (2012) Interkingdom metabolic transformations captured by microbial imaging mass spectrometry. Proc Natl Acad Sci U S A 109:13811–13816
Moroji T, Takahashi K, Ogura K, Toishi T, Arai S (1977) Rapid microwave fixation of rat brain. J Microw Power 12:273–286
Nemes P, Vertes A (2007) Laser ablation electrospray ionization for atmospheric pressure, in vivo, and imaging mass spectrometry. Anal Chem 79:8098–8106
Patti GJ, Shriver LP, Wassif CA, Woo HK, Uritboonthai W, Apon J, Manchester M, Porter FD, Siuzdak G (2010) Nanostructure-initiator mass spectrometry (Nims) imaging of brain cholesterol metabolites in Smith-Lemli-Opitz syndrome. Neuroscience 170:858–864
Saigusa D, Okudaira M, Wang J, Kano K, Kurano M, Uranbileg B, Ikeda H, Yatomi Y, Motohashi H, Aoki J (2014) Simultaneous quantification of sphingolipids in small quantities of liver by LC-MS/MS. Mass Spectrom (Tokyo) 3:S0046
Schneider DR, Felt BT, Goldman H (1981) Microwave radiation energy: a probe for the neurobiologist. Life Sci 29:643–653
Spiegel S, Milstien S (2003) Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 4:397–407
Steinhauser ML, Bailey AP, Senyo SE, Guillermier C, Perlstein TS, Gould AP, Lee RT, Lechene CP (2012) Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism. Nature 481:516–519
Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM (2001) Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 7:493–496
Sugiura Y, Konishi Y, Zaima N, Kajihara S, Nakanishi H, Taguchi R, Setou M (2009) Visualization of the cell-selective distribution of PUFA-containing phosphatidylcholines in mouse brain by imaging mass spectrometry. J Lipid Res 50:1776–1788
Sugiura Y, Taguchi R, Setou M (2011) Visualization of spatiotemporal energy dynamics of hippocampal neurons by mass spectrometry during a Kainate-Induced Seizure. Plos One 6:e17952. doi:10.1371/journal.pone.0017952
Sugiura Y, Zaima N, Setou M, Ito S, Yao I (2012) Visualization of acetylcholine distribution in central nervous system tissue sections by tandem imaging mass spectrometry. Anal Bioanal Chem 403:1851–1861
Sugiura Y, Honda K, Kajimura M, Suematsu M (2014) Visualization and quantification of cerebral metabolic fluxes of glucose in awake mice. Proteomics 14:829–838
Svensson M, Boren M, Skold K, Falth M, Sjogren B, Andersson M, Svenningsson P, Andren PE (2009) Heat stabilization of the tissue proteome: a new technology for improved proteomics. J Proteome Res 8:974–981
Taira S, Sugiura Y, Moritake S, Shimma S, Ichiyanagi Y, Setou M (2008) Nanoparticle-assisted laser desorption/ionization based mass imaging with cellular resolution. Anal Chem 80:4761–4766
Takahashi T, Ohnishi H, Sugiura Y, Honda K, Suematsu M, Kawasaki T, Deguchi T, Fujii T, Orihashi K, Hippo Y, Watanabe T, Yamagaki T, Yuba S (2014) Non-neuronal acetylcholine as an endogenous regulator of proliferation and differentiation of Lgr5-positive stem cells in mice. Febs J 281:4672–4690
Takeda A, Kobayashi D, Aoi K, Sasaki N, Sugiura Y, Igarashi H, Tohya K, Inoue A, Hata E, Akahoshi N, Hayasaka H, Kikuta J, Scandella E, Ludewig B, Ishii S, Aoki J, Suematsu M, Ishii M, Takeda K, Jalkanen S, Miyasaka M, Umemoto E (2016) Fibroblastic reticular cell-derived lysophosphatidic acid regulates confined intranodal T-cell motility. Elife 5:e10561. doi:10.7554/eLife.10561
Takenouchi T, Sugiura Y, Morikawa T, Nakanishi T, Nagahata Y, Sugioka T, Honda K, Kubo A, Hishiki T, Matsuura T, Hoshino T, Takahashi T, Suematsu M, Kajimura M (2015) Therapeutic hypothermia achieves neuroprotection via a decrease in acetylcholine with a concurrent increase in carnitine in the neonatal hypoxia-ischemia. J Cerebr Blood F Met 35:794–805
Toue S, Sugiura Y, Kubo A, Ohmura M, Karakawa S, Mizukoshi T, Yoneda J, Miyano H, Noguchi Y, Kobayashi T, Kabe Y, Suematsu M (2014) Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts. Proteomics 14:810–819
Wiseman JM, Ifa DR, Zhu YX, Kissinger CB, Manicke NE, Kissinger PT, Cooks RG (2008) Desorption electrospray ionization mass spectrometry: imaging drugs and metabolites in tissues. Proc Natl Acad Sci U S A 105:18120–18125
Wymann MP, Schneiter R (2008) Lipid signalling in disease. Nat Rev Mol Cell Biol 9:162–176
Yuki D, Sugiura Y, Zaima N, Akatsu H, Takei S, Yao I, Maesako M, Kinoshita A, Yamamoto T, Kon R, Sugiyama K, Setou M (2014) DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer’s disease. Sci Rep 4:7130. doi:10.1038/srep07130
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Sugiura, Y., Honda, K., Suematsu, M. (2016). Visualization of Localized Cellular Signalling Mediators in Tissues by Imaging Mass Spectrometry. In: Miyasaka, M., Takatsu, K. (eds) Chronic Inflammation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56068-5_12
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