title: The perforin mediated apoptotic pathway in lung injury and fibrosis.
abstract: OBJECTIVE
  The perforin mediated pathway is the major pathway of cytotoxicity induced by activated T cells and natural killer cells, and may be involved in the development of pulmonary fibrosis.
  
  
  METHODS
  Perforin and granzyme B expression were examined in idiopathic pulmonary fibrosis by means of immunohistochemistry, and perforin knockout mice were used to examine whether or not perforin mediated cytotoxicity participates in the pathophysiology of bleomycin induced pneumopathy.
  
  
  RESULTS
  Perforin and granzyme B expression were upregulated in infiltrating lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis compared with normal lung parenchyma. Perforin and granzyme B expression were upregulated predominantly in infiltrating mononuclear cells after bleomycin instillation in wild-type mice. Although the development of bleomycin induced pneumopathy was not completely prevented, the pathological grade of inflammation and fibrosis, and the number of apoptotic cells in lung tissue, were significantly decreased in perforin knockout mice compared with wild-type mice.
  
  
  CONCLUSIONS
  These results suggest that perforin mediated apoptosis may be associated with the pathophysiology of lung injury and fibrosis.
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Miyazaki
authors.forename: K
authors.initials: K
authors.lastname: Kuwano
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Maeyama
authors.forename: M
authors.initials: M
authors.lastname: Yoshimi
authors.forename: M
authors.initials: M
authors.lastname: Fujita
authors.forename: N
authors.initials: N
authors.lastname: Hagimoto
authors.forename: R
authors.initials: R
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D001761:Bleomycin; D003602:Cytotoxicity, Immunologic / Q000276:immunology / Q000502:physiology; D004195:Disease Models, Animal; D053804:Granzymes; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology / Q000502:physiology
chemical_list: D000964:Antimetabolites, Antineoplastic; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D001761:Bleomycin; D054353:Perforin; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases