Effects of mucoid and non-mucoid Pseudomonas aeruginosa isolates from cystic fibrosis patients on inflammatory mediator release from human polymorphonuclear granulocytes and rat mast cells

Mucoid Pseudomonas aeruginosa causing chronic bronchopulmonary infection in cystic fibrosis (CF) patients may interfere with host defence mechanisms. We investigated 13 P. aeruginosa strains isolated from sputa of CF patients with regard to the induction or modulation of inflammatory mediator release from human neutrophils (PMN) and rat mast cells. The effects of mucoid as compared to non-mucoid bacteria were studied using a mucoid strain and its non-mucoid revertant. The release of leukotrienes (LT) and histamine in response to the majority of the CF strains was insignificant. However, preincubation of PMN with P. aeruginosa caused a dose-dependent decrease (50-95%) of LTB₄ and LTC₄ generation and LTB₄ metabolism induced by the Ca²⁺-ionophore A23187 or opsonized zymosan (ZX) (P < 0.001). The mucoid strains caused a three- to 10-fold higher impairment of LTB₄ release (P < 0.05) and a concomitant down-regulation of LTB₄ receptors on neutrophils. Inhibitory effects were also obtained for mucoid and non-mucoid bacteria when the phorbol-ester or the Ca²⁺-ionophore induced luminol enhanced chemiluminescence response (P < 0.001) or the histamine release from rat peritoneal mast cells (P < 0.01) was studied. The bacteria-cell contact with non-mucoid strains was associated with an increased Ca²⁺ influx into PMN, whereas mucoid bacteria had no effect. In addition, a protein kinase C-dependent decrease of the C3b(i) receptor was suppressed by the mucoid- and less effectively-by the non-mucoid strain. The results suggest that the impairment of the phagocytic and inflammatory system may contribute to the pathogenesis and persistence of mucoid P. aeruginosa infection in CF.