title: Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor.
abstract: Secretory leukocyte protease inhibitor (SLPI) has multiple functions, including inhibition of protease activity, microbial growth, and inflammatory responses. In this study, we demonstrate that mouse SLPI is critically involved in innate host defense against pulmonary mycobacterial infection. During the early phase of respiratory infection with Mycobacterium bovis bacillus Calmette-Guérin, SLPI was produced by bronchial and alveolar epithelial cells, as well as alveolar macrophages, and secreted into the alveolar space. Recombinant mouse SLPI effectively inhibited in vitro growth of bacillus Calmette-Guérin and Mycobacterium tuberculosis through disruption of the mycobacterial cell wall structure. Each of the two whey acidic protein domains in SLPI was sufficient for inhibiting mycobacterial growth. Cationic residues within the whey acidic protein domains of SLPI were essential for disruption of mycobacterial cell walls. Mice lacking SLPI were highly susceptible to pulmonary infection with M. tuberculosis. Thus, mouse SLPI is an essential component of innate host defense against mycobacteria at the respiratory mucosal surface.
authors.affiliation: Deparment of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Saiga
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.forename: Megumi
authors.initials: M
authors.lastname: Okuyama
authors.forename: Hisako
authors.initials: H
authors.lastname: Kayama
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kuwata
authors.forename: Sohkichi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000276:immunology / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D017434:Protein Structure, Tertiary; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014397:Tuberculosis, Pulmonary / Q000201:enzymology / Q000276:immunology / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D006131:Growth Inhibitors; D053481:Secretory Leukocyte Peptidase Inhibitor