title: 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: 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.
authors.affiliation: Department of Surgical Oncology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. kemori-tky@umin.ac.jp
authors.forename: Ken
authors.initials: K
authors.lastname: Mori
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kishi
authors.forename: Dai
authors.initials: D
authors.lastname: Shida
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Yamashita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D053818:Chymases / Q000032:analysis; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000096:biosynthesis*; D008407:Mast Cells / Q000145:classification / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D043264:Phosphodiesterase I / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D010727:Phosphoric Diester Hydrolases / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D011755:Pyrophosphatases / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D053802:Tryptases / Q000032:analysis; D014945:Wound Healing; D000099189:Lysophospholipase D
chemical_list: D053818:Chymases; D008246:Lysophospholipids; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D053802:Tryptases; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid