title: Pleural mesothelial cells modulate polymorphonuclear leukocyte apoptosis in empyema.
abstract: In bacterial empyema, the recruited polymorphonuclear leukocytes (PMN) represent important phagocytic cells involved in antibacterial defense. In this study we demonstrate that pleural fluids (PF) obtained from patients with empyema (EMP) contains significantly higher levels of granulocyte colony stimulating factor (GM-CSF), and PMN incubated in empyema (EMP) pleural fluid (PF) showed significantly less apoptosis than congestive heart failure (CHF) PF. Staphylococcus aureus-stimulated PMC released significantly (P < 0.001) higher levels of GM-CSF than resting PMC. Staphylococcus aureus-stimulated PMC (SPMC)-CM significantly (P < 0.001) inhibited PMN apoptosis. In SPMC-CM-incubated PMN the antiapoptotic gene Bcl-xL mRNA and protein expression was up-regulated; Bak mRNA and protein expression was down-regulated compared to control PMN. The active caspases activity significantly decreased. When SPMC-CM and EMP PF were immunodepleted with GM-CSF antibody, PMN apoptosis was significantly higher. The delay in apoptosis of PMN is in part attributable to the release of cytokine GM-CSF by activated PMC. These findings suggest that S. aureus-activated PMC extend PMN life span by modulating Bcl-xL and Bak gene expression and active caspases activity during acute inflammation and empyema.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Veterans' Affairs Medical Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Najmunnisa
authors.initials: N
authors.lastname: Nasreen
authors.forename: Kamal A
authors.initials: KA
authors.lastname: Mohammed
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Sanders
authors.forename: Joyce
authors.initials: J
authors.lastname: Hardwick
authors.forename: Robert D
authors.initials: RD
authors.lastname: Van Horn
authors.forename: Ramit K
authors.initials: RK
authors.lastname: Sharma
authors.forename: Mun
authors.initials: M
authors.lastname: Kilani
authors.forename: Veena B
authors.initials: VB
authors.lastname: Antony
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D016724:Empyema, Pleural / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D035422:Pleural Cavity / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein
chemical_list: C494772:BAK1 protein, human; C494811:BCL2L1 protein, human; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020169:Caspases