title: Group B Streptococcus induces a caspase-dependent apoptosis in fetal rat lung interstitium.
abstract: Group B Streptococcus (GBS) is an important pathogen and is associated with sepsis and meningitis in neonates and infants. An ex vivo model that facilitates observations of GBS interactions with multiple host cell types over time was used to study its pathogenicity. GBS infections were associated with profound reductions in fetal lung; explant size, and airway branching. Elevated levels of apoptosis subsequent to GBS infections were observed by whole-mount confocal immunofluorescence using activated-caspase-3-antibodies and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assays. The caspase inhibitor Z-VAD-FMK abolished the increase in TUNEL-positive cells associated with GBS infections, indicating that the GBS-induced apoptosis was caspase-dependent. Digital image analyses revealed that both GBS and the active form of caspase-3 were distributed primarily within the lung interstitium, suggesting that these tissues are important targets for GBS. Antibodies to the active form of caspase-3 colocalized with both macrophage- and erythroblast-markers, suggesting that these hematopoietic cells are vulnerable to GBS-mediated pathogenesis. These studies suggest that GBS infections profoundly alter lung morphology and caspase-dependent hematopoietic cell apoptosis within the lung interstitium play roles in GBS pathophysiology in this model.
authors.affiliation: Boston College Department of Biology, 140 Commonwealth Avenue, Higgins #430, Chestnut Hill, MA 02467, USA. klingd@bc.edu
authors.forename: David E
authors.initials: DE
authors.lastname: Kling
authors.forename: Inna
authors.initials: I
authors.lastname: Tsvang
authors.forename: Miriam P
authors.initials: MP
authors.lastname: Murphy
authors.forename: David S
authors.initials: DS
authors.lastname: Newburg
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013290:Streptococcal Infections / Q000473:pathology* / Q000503:physiopathology; D013292:Streptococcus agalactiae / Q000472:pathogenicity*
chemical_list: D053148:Caspase 3
keywords: Ex vivo; Gram-positive; Quantitative colocalization; Respiratory; Sepsis; Streptococcus agalactiae