sepharose and Pseudomonas-Infections

The implementation of non-traditional antibacterials is currently one of the most intensively explored areas of modern medical and biological sciences. One of the most promising alternative strategies to combat bacterial infections is the application of lytic phages combined with established and new antibacterials. The presented study investigates the potential of agarose-based biocomposites containing lytic Pseudomonas phages (KT28, KTN4, and LUZ19), cupric ions (Cu

Topics: Anti-Bacterial Agents; Bacteriophages; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Pseudomonas Phages; Sepharose

Patients with cystic fibrosis (CF) develop chronic Pseudomonas aeruginosa lung infection with mucoid strains of P. aeruginosa; these infections cause significant morbidity. The immunological response in these infections is characterized by an influx of neutrophils to the lung and subsequent lung damage over time; however, the underlying mediators to this response are not well understood. We recently reported that IL-23 and IL-17 were elevated in the sputum of patients with CF who were actively infected with P. aeruginosa; however, the importance of IL-23 and IL-17 in mediating this inflammation was unclear. To understand the role that IL-23 plays in initiating airway inflammation in response to P. aeruginosa, IL-23p19(-/-) (IL-23 deficient) and wild-type (WT) mice were challenged with agarose beads containing a clinical, mucoid isolate of P. aeruginosa. Levels of proinflammatory cytokines, chemokines, bacterial dissemination, and inflammatory infiltrates were measured. IL-23-deficient mice had significantly lower induction of IL-17, keratinocyte-derived chemokine (KC), and IL-6, decreased bronchoalveolar lavage (BAL) neutrophils, metalloproteinase-9 (MMP-9), and reduced airway inflammation than WT mice. Despite the reduced level of inflammation in IL-23p19(-/-) mice, there were no differences in the induction of TNF and interferon-gamma or in bacterial dissemination between the two groups. This study demonstrates that IL-23 plays a critical role in generating airway inflammation observed in mucoid P. aeruginosa infection and suggests that IL-23 could be a potential target for immunotherapy to treat airway inflammation in CF.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cell Count; Chemokines; Colony Count, Microbial; Gene Expression Regulation; Glycosaminoglycans; Inflammation; Interleukin-17; Interleukin-23; Lung; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Microspheres; Pseudomonas aeruginosa; Pseudomonas Infections; RNA, Messenger; Sepharose

A model of chronic pulmonary infection was used for studying cellular events in a sequential manner. In this model, agarose beads containing Pseudomonas aeruginosa were instilled endotracheally into cats. Nine cats were inoculated with agarose beads containing P. aeruginosa, and four others were inoculated with sterile beads. With a fiberoptic bronchoscope, bronchial washings were obtained biweekly for up to 30 weeks. The quantitative pulmonary inflammatory cell response and alveolar macrophage morphology of the animals exposed to P. aeruginosa were compared with those for the animals exposed to a chronic irritant (agarose beads). Bronchial washings of all animals before inoculation showed that 70 to 90% of the cells were macrophages. After inoculation with P. aeruginosa, a persistent inflammatory response was observed (60 to 70% granulocytes). In the sterile-bead-inoculated group, the response was less prominent (30 to 40% granulocytes). As early as 2 weeks after inoculation, alveolar macrophages from infected animals were larger and had cytoplasmic features that differed from those of controls. Electron microscope examination showed prominent surface alterations in alveolar macrophages from the infected cats. These alterations persisted from 2 to 12 weeks after infection. In animals inoculated with sterile beads, alveolar macrophages exhibited less extensive surface changes that had resolved by week 8. Histologically, chronic bronchiolitis and pneumonia were more severe in the infected animals than in controls. This model of chronic inflammation and macrophage stimulation, which is similar to the chronic pneumonia of cystic fibrosis, may be a useful approach to answer questions on the role of macrophage activation in chronic lung disease.

Topics: Animals; Cats; Female; Inflammation; Leukocyte Count; Macrophages; Male; Microscopy, Electron; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Sepharose