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01.07.2007 | Original Article

Submucosal connective tissue-type mast cells contribute to the production of lysophosphatidic acid (LPA) in the gastrointestinal tract through the secretion of autotaxin (ATX)/lysophospholipase D (lysoPLD)

verfasst von: Ken Mori, Joji Kitayama, Junken Aoki, Yasuhiro Kishi, Dai Shida, Hiroharu Yamashita, Hiroyuki Arai, Hirokazu Nagawa

Erschienen in: Virchows Archiv | Ausgabe 1/2007

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Abstract

Lysophosphatidic acid (LPA) is involved in a broad spectrum of biological activities, including wound healing and cancer metastasis. Autotaxin (ATX), originally isolated from a melanoma supernatant as a tumor cell motility-stimulating factor, has been shown to be molecularly identical to lysophospholipase D (lysoPLD), which is the main enzyme in the production of LPA. Although ATX/lysoPLD is known to be widely expressed in normal human tissues, the exact distribution of ATX-producing cells has not been fully investigated. In this study, we evaluated ATX/lysoPLD expression by immunohistochemical staining using a rat anti-ATX mAb in the human gastrointestinal tract and found that submucosal mast cells (MC) highly expressed this enzyme. This was confirmed by immunofluorescent double staining using mAbs to tryptase and chymase. Then, we isolated MC from human gastric tissue by an immunomagnetic method using CD117-microbeads and showed that a subpopulation of CD203c-positive MC showed positive staining for intracellular ATX/lysoPLD on flowcytometry. This was confirmed by Western blotting of the isolated cells. Moreover, a significant level of ATX/lysoPLD release could be detected in the culture supernatants of human MC by Western blot analysis. Our data suggest that submucosal MC play significant roles in various aspects of pathophysiology in the gastrointestinal tract by locally providing bioactive LPA through the production of ATX/lysoPLD.

Aldenborg F, Enerback L (1994) The immunohistochemical demonstration of chymase and tryptase in human intestinal mast cells. Histochem J 267:587–596CrossRef

An S, Bleu T, Hallmark OG, Goetzl EJ (1998) Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. J Biol Chem 27314:7906–7910CrossRef

Aoki J, Taira A, Takanezawa Y, Kishi Y, Hama K, Kishimoto T, Mizuno K, Saku K, Taguchi R, Arai H (2002) Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J Biol Chem 27750:48737–48744CrossRef

Bandoh K, Aoki J, Hosono H, Kobayashi S, Kobayashi T, Murakami-Murofushi K, Tsujimoto M, Arai H, Inoue K (1999) Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid. J Biol Chem 27439:27776–27785CrossRef

Baumforth KR, Flavell JR, Reynolds GM, Davies G, Pettitt TR, Wei W, Morgan S, Stankovic T, Kishi Y, Arai H, Nowakova M, Pratt G, Aoki J, Wakelam MJ, Young LS, Murray PG (2005) Induction of autotaxin by the Epstein–Barr virus promotes the growth and survival of Hodgkin’s lymphoma cells. Blood 106(6):2138–2146PubMedCrossRef

Bischoff SC (1996) Mucosal allergy: role of mast cells and eosinophil granulocytes in the gut. Baillieres Clin Gastroenterol 103:443–459CrossRef

Bischoff SC, Lorentz A, Schwengberg S, Weier G, Raab R, Manns MP (1999) Mast cells are an important cellular source of tumour necrosis factor alpha in human intestinal tissue. Gut 445:643–652CrossRef

Bischoff SC, Schwengberg S, Wordelmann K, Weimann A, Raab R, Manns MP (1996) Effect of c-kit ligand, stem cell factor, on mediator release by human intestinal mast cells isolated from patients with inflammatory bowel disease and controls. Gut 381:104–114CrossRef

Bollen M, Gijsbers R, Ceulemans H, Stalmans W, Stefan C (2000) Nucleotide pyrophosphatases/phosphodiesterases on the move. Crit Rev Biochem Mol Biol 356:393–432CrossRef

10.

Chettibi S, Lawrence AJ, Stevenson RD, Young JD (1994) Effect of lysophosphatidic acid on motility, polarisation and metabolic burst of human neutrophils. FEMS Immunol Med Microbiol 83:271–281CrossRef

11.

Contos JJ, Fukushima N, Weiner JA, Kaushal D, Chun J (2000) Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. Proc Natl Acad Sci USA 9724:13384–13389CrossRef

12.

Croset M, Brossard N, Polette A, Lagarde M (2000) Characterization of plasma unsaturated lysophosphatidylcholines in human and rat. Biochem J 345(Pt 1):61–67PubMedCrossRef

13.

Fang X, Yu S, Bast RC, Liu S, Xu HJ, Hu SX, LaPushin R, Claret FX, Aggarwal BB, Lu Y, Mills GB (2004) Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian cancer cells. J Biol Chem 27910:9653–9661CrossRef

14.

Galli SJ (2000) Mast cells and basophils. Curr Opin Hematol 71:32–39CrossRef

15.

Galli SJ (1993) New concepts about the mast cell. N Engl J Med 3284:257–265CrossRef

16.

Gebhardt T, Lorentz A, Detmer F, Trautwein C, Bektas H, Manns MP, Bischoff SC (2005) Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor beta1. Gut 547:928–934CrossRef

17.

Ghannadan M, Hauswirth AW, Schernthaner GH, Muller MR, Klepetko W, Schatzl G, Sperr WR, Buhring HJ, Valent P (2002) Detection of novel CD antigens on the surface of human mast cells and basophils. Int Arch Allergy Immunol 1274:299–307CrossRef

18.

Goding JW, Grobben B, Slegers H (2003) Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. Biochim Biophys Acta 16381:1–19

19.

Goetzl EJ, An S (1998) Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1-phosphate. FASEB J 1215:1589–1598

20.

Goetzl EJ, Kong Y, Voice JK (2000) Cutting edge: differential constitutive expression of functional receptors for lysophosphatidic acid by human blood lymphocytes. J Immunol 16410:4996–4999

21.

Goldstein SM, Kaempfer CE, Kealey JT, Wintroub BU (1989) Human mast cell carboxypeptidase. Purification and characterization. J Clin Invest 835:1630–1636CrossRef

22.

Gschwind A, Hart S, Fischer OM, Ullrich A (2003) TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells. EMBO J 2210:2411–2421CrossRef

23.

He SH (2004) Key role of mast cells and their major secretory products in inflammatory bowel disease. World J Gastroenterol 103:309–318

24.

Hecht JH, Weiner JA, Post SR, Chun J (1996) Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. J Cell Biol 1354:1071–1083CrossRef

25.

Hines OJ, Ryder N, Chu J, McFadden D (2000) Lysophosphatidic acid stimulates intestinal restitution via cytoskeletal activation and remodeling. J Surg Res 921:23–28CrossRef

26.

Holgate ST (2000) The role of mast cells and basophils in inflammation. Clin Exp Allergy 30(Suppl 1):28–32PubMedCrossRef

27.

Irani AM, Bradford TR, Kepley CL, Schechter NM, Schwartz LB (1989) Detection of MCT and MCTC types of human mast cells by immunohistochemistry using new monoclonal anti-tryptase and anti-chymase antibodies. J Histochem Cytochem 3710:1509–1515

28.

Irani AM, Craig SS, DeBlois G, Elson CO, Schechter NM, Schwartz LB (1987) Deficiency of the tryptase-positive, chymase-negative mast cell type in gastrointestinal mucosa of patients with defective T lymphocyte function. J Immunol 13812:4381–4386

29.

Irani AM, Goldstein SM, Wintroub BU, Bradford T, Schwartz LB (1991) Human mast cell carboxypeptidase. Selective localization to MCTC cells. J Immunol 1471:247–253

30.

Johnson RG, Carty SE, Fingerhood BJ, Scarpa A (1980) The internal pH of mast cell granules. FEBS Lett 1201:75–79CrossRef

31.

Kitayama J, Shida D, Sako A, Ishikawa M, Hama K, Aoki J, Arai H, Nagawa H (2004) Over-expression of lysophosphatidic acid receptor-2 in human invasive ductal carcinoma. Breast Cancer Res 66:R640–R646CrossRef

32.

Kondo K, Muramatsu M, Okamoto Y, Jin D, Takai S, Tanigawa N, Miyazaki M (2006) Expression of chymase-positive cells in gastric cancer and its correlation with the angiogenesis. J Surg Oncol 931:36–42; discussion 42–33CrossRef

33.

Mekori YA, Metcalfe DD (2000) Mast cells in innate immunity. Immunol Rev 173:131–140PubMedCrossRef

34.

Mills GB, Moolenaar WH (2003) The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer 38:582–591CrossRef

35.

Moolenaar WH (1995) Lysophosphatidic acid, a multifunctional phospholipid messenger. J Biol Chem 27022:12949–12952

36.

Murata J, Lee HY, Clair T, Krutzsch HC, Arestad AA, Sobel ME, Liotta LA, Stracke ML (1994) cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases. J Biol Chem 26948:30479–30484

37.

Nam SW, Clair T, Campo CK, Lee HY, Liotta LA, Stracke ML (2000) Autotaxin (ATX), a potent tumor motogen, augments invasive and metastatic potential of ras-transformed cells. Oncogene 192:241–247CrossRef

38.

Nam SW, Clair T, Kim YS, McMarlin A, Schiffmann E, Liotta LA, Stracke ML (2001) Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. Cancer Res 6118:6938–6944

39.

Okayama Y, Hunt TC, Kassel O, Ashman LK, Church MK (1994) Assessment of the anti-c-kit monoclonal antibody YB5.B8 in affinity magnetic enrichment of human lung mast cells. J Immunol Methods 1692:153–161CrossRef

40.

Palmetshofer A, Robson SC, Nehls V (1999) Lysophosphatidic acid activates nuclear factor kappa B and induces proinflammatory gene expression in endothelial cells. Thromb Haemost 825:1532–1537

41.

Panetti TS, Nowlen J, Mosher DF (2000) Sphingosine-1-phosphate and lysophosphatidic acid stimulate endothelial cell migration. Arterioscler Thromb Vasc Biol 204:1013–1019

42.

Pedotti R, De Voss JJ, Steinman L, Galli SJ (2003) Involvement of both ‘allergic’ and ‘autoimmune’ mechanisms in EAE, MS and other autoimmune diseases. Trends Immunol 249:479–484CrossRef

43.

Rahaman M, Costello RW, Belmonte KE, Gendy SS, Walsh MT (2006) Neutrophil sphingosine 1-phosphate and lysophosphatidic acid receptors in pneumonia. Am J Respir Cell Mol Biol 342:233–241CrossRef

44.

Ribatti D, Ennas MG, Vacca A, Ferreli F, Nico B, Orru S, Sirigu P (2003) Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma. Eur J Clin Invest 335:420–425CrossRef

45.

Rizza C, Leitinger N, Yue J, Fischer DJ, Wang DA, Shih PT, Lee H, Tigyi G, Berliner JA (1999) Lysophosphatidic acid as a regulator of endothelial/leukocyte interaction. Lab Invest 7910:1227–1235

46.

Savaskan NE, Rocha L, Kotter MR, Baer A, Lubec G, van Meeteren LA, Kishi Y, Aoki J, Moolenaar WH, Nitsch R, Brauer AU (2007) Autotaxin (NPP-2) in the brain: cell type-specific expression and regulation during development and after neurotrauma. Cell Mol Life Sci 642:230–243CrossRef

47.

Segura BJ, Zhang W, Cowles RA, Xiao L, Lin TR, Logsdon C, Mulholland MW (2004) Lysophosphatidic acid stimulates calcium transients in enteric glia. Neuroscience 1233:687–693CrossRef

48.

Sengupta S, Wang Z, Tipps R, Xu Y (2004) Biology of LPA in health and disease. Semin Cell Dev Biol 155:503–512CrossRef

49.

Shah PM, Husby S, Damsgaard TE, Nielsen HV, Schiotz PO (1998) Purification of human colonic and gastric mast cells. J Immunol Methods 214:141–148PubMedCrossRef

50.

Shida D, Kitayama J, Yamaguchi H, Hama K, Aoki J, Arai H, Yamashita H, Mori K, Sako A, Konishi T, Watanabe T, Sakai T, Suzuki R, Ohta H, Takuwa Y, Nagawa H (2004) Dual mode regulation of migration by lysophosphatidic acid in human gastric cancer cells. Exp Cell Res 3012:168–178CrossRef

51.

Shida D, Kitayama J, Yamaguchi H, Okaji Y, Tsuno NH, Watanabe T, Takuwa Y, Nagawa H (2003) Lysophosphatidic acid (LPA) enhances the metastatic potential of human colon carcinoma DLD1 cells through LPA1. Cancer Res 637:1706–1711

52.

Shida D, Watanabe T, Aoki J, Hama K, Kitayama J, Sonoda H, Kishi Y, Yamaguchi H, Sasaki S, Sako A, Konishi T, Arai H, Nagawa H (2004) Aberrant expression of lysophosphatidic acid (LPA) receptors in human colorectal cancer. Lab Invest 8410:1352–1362CrossRef

53.

Stassar MJ, Devitt G, Brosius M, Rinnab L, Prang J, Schradin T, Simon J, Petersen S, Kopp-Schneider A, Zoller M (2001) Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization. Br J Cancer 859:1372–1382CrossRef

54.

Stefan C, Jansen S, Bollen M (2005) NPP-type ectophosphodiesterases: unity in diversity. Trends Biochem Sci 3010:542–550CrossRef

55.

Stracke M, Liotta LA, Schiffmann E (1993) The role of autotaxin and other motility stimulating factors in the regulation of tumor cell motility. Symp Soc Exp Biol 47:197–214PubMed

56.

Stracke ML, Clair T, Liotta LA (1997) Autotaxin, tumor motility-stimulating exophosphodiesterase. Adv Enzyme Regul 37:135–144PubMedCrossRef

57.

Stracke ML, Krutzsch HC, Unsworth EJ, Arestad A, Cioce V, Schiffmann E, Liotta LA (1992) Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem 2674:2524–2529

58.

Sturm A, Sudermann T, Schulte KM, Goebell H, Dignass AU (1999) Modulation of intestinal epithelial wound healing in vitro and in vivo by lysophosphatidic acid. Gastroenterology 1172:368–377CrossRef

59.

Sturm A, Zeeh J, Sudermann T, Rath H, Gerken G, Dignass AU (2002) Lisofylline and lysophospholipids ameliorate experimental colitis in rats. Digestion 661:23–29CrossRef

60.

Tanaka M, Kishi Y, Takanezawa Y, Kakehi Y, Aoki J, Arai H (2004) Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma. FEBS Lett 571:197–204PubMedCrossRef

61.

Thies F, Delachambre MC, Bentejac M, Lagarde M, Lecerf J (1992) Unsaturated fatty acids esterified in 2-acyl-l-lysophosphatidylcholine bound to albumin are more efficiently taken up by the young rat brain than the unesterified form. J Neurochem 593:1110–1116CrossRef

62.

Tokumura A, Fujimoto H, Yoshimoto O, Nishioka Y, Miyake M, Fukuzawa K (1999) Production of lysophosphatidic acid by lysophospholipase D in incubated plasma of spontaneously hypertensive rats and Wistar Kyoto rats. Life Sci 653:245–253CrossRef

63.

Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, Fukuzawa K (2002) Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem 27742:39436–39442CrossRef

64.

Tokumura A, Tominaga K, Yasuda K, Kanzaki H, Kogure K, Fukuzawa K (2002) Lack of significant differences in the corrected activity of lysophospholipase D, producer of phospholipid mediator lysophosphatidic acid, in incubated serum from women with and without ovarian tumors. Cancer 941:141–151CrossRef

65.

Tomita M, Matsuzaki Y, Edagawa M, Shimizu T, Hara M, Sekiya R, Onitsuka T (2001) Association of mast cells with tumor angiogenesis in esophageal squamous cell carcinoma. Dis Esophagus 142:135–138CrossRef

66.

Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, Yamori T, Mills GB, Inoue K, Aoki J, Arai H (2002) Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol 1582:227–233CrossRef

67.

Umezu-Goto M, Tanyi J, Lahad J, Liu S, Yu S, Lapushin R, Hasegawa Y, Lu Y, Trost R, Bevers T, Jonasch E, Aldape K, Liu J, James RD, Ferguson CG, Xu Y, Prestwich GD, Mills GB (2004) Lysophosphatidic acid production and action: validated targets in cancer? J Cell Biochem 926:1115–1140CrossRef

68.

von Boyen GB, Steinkamp M, Reinshagen M, Schafer KH, Adler G, Kirsch J (2004) Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia. Gut 532:222–228CrossRef

69.

Walls AF, Jones DB, Williams JH, Church MK, Holgate ST (1990) Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase. J Pathol 1622:119–126CrossRef

70.

Yang SY, Lee J, Park CG, Kim S, Hong S, Chung HC, Min SK, Han JW, Lee HW, Lee HY (2002) Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells. Clin Exp Metastasis 197:603–608CrossRef

71.

Yang Y, Mou L, Liu N, Tsao MS (1999) Autotaxin expression in non-small-cell lung cancer. Am J Respir Cell Mol Biol 212:216–222

72.

Zhang G, Zhao Z, Xu S, Ni L, Wang X (1999) Expression of autotaxin mRNA in human hepatocellular carcinoma. Chin Med J (Engl) 1124:330–332

73.

Zheng Y, Voice JK, Kong Y, Goetzl EJ (2000) Altered expression and functional profile of lysophosphatidic acid receptors in mitogen-activated human blood T lymphocytes. FASEB J 1415:2387–2389

Titel: Submucosal connective tissue-type mast cells contribute to the production of lysophosphatidic acid (LPA) in the gastrointestinal tract through the secretion of autotaxin (ATX)/lysophospholipase D (lysoPLD)
verfasst von: Ken Mori
Joji Kitayama
Junken Aoki
Yasuhiro Kishi
Dai Shida
Hiroharu Yamashita
Hiroyuki Arai
Hirokazu Nagawa
Publikationsdatum: 01.07.2007
Verlag: Springer-Verlag
Erschienen in: Virchows Archiv / Ausgabe 1/2007
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-007-0425-4

Springer Medizin

Submucosal connective tissue-type mast cells contribute to the production of lysophosphatidic acid (LPA) in the gastrointestinal tract through the secretion of autotaxin (ATX)/lysophospholipase D (lysoPLD)

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

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