title: Activation of the granzyme pathway in children with severe respiratory syncytial virus infection.
abstract: Granzymes (Grs), serine proteases present in granules of effector lymphocytes, are involved in several host immune responses, including the activation of cell death and inflammatory pathways. The main goal of this study was to determine whether the local cell-mediated Gr pathway is activated during severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in children. Tracheal aspirates (TA) from 23 children with RSV-LRTI and 12 controls without pulmonary disease were analyzed for Gr A and B. Bronchoalveolar lavage fluid samples from seven children with RSV-LRTI were analyzed for cellular expression of GrB. Levels of GrA and GrB in TA were significantly increased in RSV patients compared with controls and both Grs showed preserved activity. Gr levels correlated with the total leukocyte counts and IL-8 levels in the airways at several time points. However, no correlation between Gr levels and release of caspase-cleaved cytokeratin-18 was found. There was evidence for marked expression of GrB by both CD8(+) and CD4(+) T cells and natural killer cells in the respiratory tract. These findings suggest activation of the cell-mediated Gr pathway during severe RSV-LRTI in children.
authors.affiliation: Pediatric Intensive Care Unit, Academic Medical Center, Amsterdam, 1100 DD, The Netherlands. r.a.bem@amc.uva.nl
authors.forename: Reinout A
authors.initials: RA
authors.lastname: Bem
authors.forename: Albert P
authors.initials: AP
authors.lastname: Bos
authors.forename: Michael
authors.initials: M
authors.lastname: Bots
authors.forename: Angela M
authors.initials: AM
authors.lastname: Wolbink
authors.forename: S Marieke
authors.initials: SM
authors.lastname: van Ham
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Medema
authors.forename: Rene
authors.initials: R
authors.lastname: Lutter
authors.forename: Job B M
authors.initials: JB
authors.lastname: van Woensel
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007231:Infant, Newborn; D016209:Interleukin-8 / Q000378:metabolism; D053538:Keratin-18 / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D018357:Respiratory Syncytial Virus Infections / Q000201:enzymology* / Q000276:immunology / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D012720:Severity of Illness Index; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000821:virology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D016209:Interleukin-8; C488421:KRT18 protein, human; D053538:Keratin-18; C509213:GZMB protein, human; D053804:Granzymes; C509212:GZMA protein, human