title: Lysophosphatidic acid enhances antimycobacterial activity both in vitro and ex vivo.
abstract: Lysophosphatidic acid (LPA) is a polar lipid metabolite which is involved in a wide range of biological processes, including cell proliferation and migration, wound healing, and increase of endothelial permeability. The present study reports evidences showing that LPA is able to enhance the antimicrobial activity of human macrophages and of bronchoalveolar lavage cells from tuberculosis patients leading to intracellular growth control of Mycobacterium tuberculosis. Such antimicrobial activity is mediated by the activation of phospholipase D which in turn induces acidification of M. tuberculosis containing phagosomes and is associated with the enhanced expression of Cathepsin D. These results suggest the possible protective role of this lysophospholipid in the activation of innate antimycobacterial response.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica-00133, Rome, Italy.
authors.forename: S K
authors.initials: SK
authors.lastname: Garg
authors.forename: E
authors.initials: E
authors.lastname: Valente
authors.forename: E
authors.initials: E
authors.lastname: Greco
authors.forename: M B
authors.initials: MB
authors.lastname: Santucci
authors.forename: M
authors.initials: M
authors.lastname: De Spirito
authors.forename: M
authors.initials: M
authors.lastname: Papi
authors.forename: M
authors.initials: M
authors.lastname: Bocchino
authors.forename: C
authors.initials: C
authors.lastname: Saltini
authors.forename: M
authors.initials: M
authors.lastname: Fraziano
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D002402:Cathepsin D / Q000096:biosynthesis; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology; D008246:Lysophospholipids / Q000502:physiology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D010739:Phospholipase D / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D000995:Antitubercular Agents; D008246:Lysophospholipids; D010739:Phospholipase D; D002402:Cathepsin D; C032881:lysophosphatidic acid