title: Immunohistochemical analysis of perforin and granzyme A in inflammatory myopathies.
abstract: Perforin (PF) and granzyme A (GA) are candidates suspected of being cytolytic proteins of the granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. We analysed PF and GA in muscles from patients with inflammatory myopathies. Five cases of polymyositis (PM), two cases of inclusion body myositis (IBM), and five cases of dermatomyositis (DM) were studied immunohistochemically using anti-PF and GA antibodies raised against each synthetic peptide of human PF and mouse GA, together with a panel of monoclonal antibodies reactive for lymphocyte subsets. In PM and IBM, PF positive cells were colocalized with GA positive cells and occasionally invaded into the non-necrotic muscle fibres. The percentage of PF positive cells among the endomysial CD8 positive cell population was 9.9% (PM) and 12.5% (IBM), and the majority of the endomysial CD8 positive cells were alpha/beta T cells. In contrast, in DM, both PF and GA positive cells were very few in all cases. Only few inflammatory cells were CD16+ or CD57+ NK cells among these diseases. Our results suggest that PF and GA are secreted mainly from alpha/beta T cells, and may play a key role in muscle fibre damage in at least some PM and IBM, but not in DM.
authors.affiliation: National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Orimo
authors.forename: R
authors.initials: R
authors.lastname: Koga
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Arai
authors.forename: M
authors.initials: M
authors.lastname: Tamaki
authors.forename: H
authors.initials: H
authors.lastname: Sugita
authors.forename: I
authors.initials: I
authors.lastname: Nonaka
authors.forename: K
authors.initials: K
authors.lastname: Arahata
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D002478:Cells, Cultured; D003882:Dermatomyositis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D053804:Granzymes; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009220:Myositis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human