Instead, immune responses contribute to the tissue damage.

However, this may depend on localization of infection in the upper conductive or in the peripheral respiratory zone. To study this we produced two distinct sizes of small alginate beads (SB) and large beads (LB) containing P. aeruginosa. In total, 175 BALB/c mice were infected with either SB or LB. At day 1 the quantitative bacteriology was higher in the SB group compared to the LB group (P < 0·003). For all time-points smaller biofilms were identified by Alcian blue staining in the SB group (P < 0·003). Similarly, the area of the airways in which biofilms were identified were smaller (P < 0·0001). A shift from exclusively endobronchial to both parenchymal PS-341 ic50 and endobronchial localization of inflammation from day 1 to days 2/3 (P < 0·05), as well as a faster resolution of inflammation at days 5/6, was observed in the SB group (P < 0·03). Finally, both the polymorphonuclear neutrophil leucocyte (PMN) mobilizer granulocyte colony-stimulating factor (G-CSF)

and chemoattractant macrophage inflammatory protein-2 (MIP-2) were increased at day 1 in the SB group (P < 0·0001). In conclusion, we have established a model enabling studies of host responses in different pulmonary zones. An effective recognition of and a more pronounced host response to infection in the peripheral zones, indicating that increased lung damage was demonstrated. Selleck Crizotinib Therefore, treatment of the chronic P. aeruginosa lung infection should be directed primarily at the peripheral lung zone by combined intravenous and inhalation antibiotic treatment. Most patients

with the inherited disease cystic fibrosis (CF) acquire a chronic lung infection with Pseudomonas aeruginosa. Once chronic P. aeruginosa lung infection is established it is almost impossible to eradicate, despite relevant antibiotic treatment and substantial innate and adaptive host responses. The background for the tolerance of the chronic P. aeruginosa Adenosine triphosphate lung infection to antibiotics and host responses is the formation of biofilms, where the bacteria are organized in micro colonies surrounded by an extracellular matrix. Because the infection remains in the lungs, continuous induction of pulmonary inflammation and stimulation of the adaptive immune response is the result. In fact, both parts of the host immune response contribute to the lung pathophysiology. The constantly recruited polymorphonuclear neutrophil leucocytes (PMNs) contribute by release of exoproteases, reactive oxygen and nitrogen species, and the induced T helper type 2 (Th2)-dominated response contributes by induction of a pronounced antibody response resulting in immune complex disease [1]. The activation and recruitment of the host response is, however, not uniform throughout the lung.