A massive accumulation of neutrophils, mainly due to enhanced interleukin-8 (IL-8) levels, is believed to contribute to the deleterious effects of lung infection, e.g., in cystic fibrosis (CF). Antibodies to phospholipase C, an exoenzyme of , are detected early and at high levels in CF patients. However, produces at least two types of phospholipase C (PLC), one haemolytic (PLC-H) and the other non-haemolytic (PLC-N), both with mol. wts of c. 77 kDa. Experiments were performed to evaluate the potential contribution of PLC to neutrophil accumulation during infection. Therefore, PLC-H and PLC-N were compared with regard to IL-8 generation from human monocytes. Purified PLC-H as well as culture supernates (mol. wt > 50 kDa) of a strain capable of producing both PLC-H and PLC-N, and mutant strains deficient in the production of one or other phospholipase, or both, were examined. Purified PLC-H (only at low concentrations up to 1 unit/4 × 10monocytes), induced a dose-dependent increase in IL-8 release and IL-8-specific mRNA expression over that of unstimulated cells (at 4-, 12- and 24-h incubation times). Higher concentrations of PLC-H led to a decrease in IL-8 release and IL-8-specific mRNA expression. These findings were confirmed by the results obtained with the supernates of cultures of mutant strains of PAO1 that produced either a PLC-H or PLC-N or neither. Stimulation and inhibition of IL-8 release and mRNA expression were associated with a culture supernate fraction of mol. wt > 50 kDa and containing PLC-H. These results contribute to the understanding of the role of both PLC in IL-8 generation during their interaction with human monocytes.


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