RAPID COMMUNICATION Lysophosphatidic acid enhances antimycobacterial activity both in vitro and ex vivo S.K. Garg a,b , E. Valente a , E. Greco a , M.B. Santucci a , M. De Spirito c , M. Papi c , M. Bocchino d,e , C. Saltini d,f , M. Fraziano a, * a Department of Biology, University of Rome bTor VergataQ, Via della Ricerca Scientifica-00133, Rome, Italy b Department of Biochemistry, University of Nebraska, Lincoln, NE 68588, USA c Institute of Physics, Catholic University of S. Hearth, Rome, Italy d Division of Respiratory Medicine of the University of Rome bTor VergataQ at the INMI bL. Spallanzani-IRCCSQ, Rome, Italy e Department of Clinical and Experimental Medicine, School of Biotechnology, University of Naples bFederico IIQ, Naples, Italy f Department of Internal Medicine, University of Rome bTor VergataQ, Rome, Italy Received 31 March 2006; accepted with revision 8 June 2006 Available online 27 July 2006 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. D 2006 Elsevier Inc. All rights reserved. Introduction Tuberculosis (TB) is one of the most dramatic pathologies in developing countries due to a single pathogen infection [1] and is responsible for about 2 million deaths each year. The dramatically increasing incidence of antibiotic resistant MTB strains has compromised both the treatment and prevention of this global disease [2]. One of the puzzling aspects of tuberculosis is that although one third of world population is infected, fewer than 10% of them develop into active disease during the first few years following exposure [3], suggesting that components of natural immune response may play an important role in the protection [4]. Thus, the understanding of the mechanisms 1521-6616/$ — see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.clim.2006.06.003 * Corresponding author. Fax: +39 6 72594224. E-mail address: fraziano@bio.uniroma2.it (M. Fraziano). KEYWORDS Mycobacterium tuberculosis ; Lysophosphatidic acid; Macrophage; Innate immunity Clinical Immunology (2006) 121, 23—28 available at www.sciencedirect.com www.elsevier.com/locate/yclim