title: Streptococcus pneumoniae induces exocytosis of Weibel-Palade bodies in pulmonary endothelial cells.
abstract: Invasive pneumococcal infections due to Streptococcus pneumoniae lead to inflammatory infiltration of leucocytes into lung alveolus, meninges and to septic dissemination within the vascular system. The lung microvasculature is covered by pulmonary endothelial cells containing Weibel-Palade bodies (WPB) releasing procoagulant von Willebrand factor (vWF) and other proteins in response to inflammatory stimuli. The influence of pathogenic pneumococci on secretion of WPB proteins is unknown. Here, we report that adherence of S. pneumoniae to primary human pulmonary microvascular endothelial cells (HPMEC) stimulates the WPB exocytosis and the secretion of vWF and interleukin 8 (IL-8). Moreover, infection analyses performed with pneumococcal mutants deficient in the expression of cytotoxic pneumolysin demonstrated that, in addition to direct bacterial adherence, sublytic concentrations of pneumolysin stimulated vWF secretion. The release of vWF was induced after infection with pneumococci from both the apical and the basal cell surfaces, which implies a stimulation of WPB exocytosis in both directions: from inside the vasculature and also following invasive pneumococcal transmigration from pulmonary tissue into the bloodstream. In conclusion, this study demonstrates that the most relevant pulmonary pathogen S. pneumoniae induces release of proinflammatory and procoagulative components directly contributing to pathophysiological processes leading to fatal tissue injury during course of infection.
authors: Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany.
authors: Melanie
authors: M
authors: Lüttge
authors: Marcus
authors: M
authors: Fulde
authors: Susanne R
authors: SR
authors: Talay
authors: Andreas
authors: A
authors: Nerlich
authors: Manfred
authors: M
authors: Rohde
authors: Klaus T
authors: KT
authors: Preissner
authors: Sven
authors: S
authors: Hammerschmidt
authors: Michael
authors: M
authors: Steinert
authors: Tim J
authors: TJ
authors: Mitchell
authors: Gursharan S
authors: GS
authors: Chhatwal
authors: Simone
authors: S
authors: Bergmann
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000633:toxicity; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism* / Q000382:microbiology*; D005089:Exocytosis; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D013301:Streptolysins / Q000633:toxicity; D020302:Weibel-Palade Bodies / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016209:Interleukin-8; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D014841:von Willebrand Factor