Activation of human effector cells by different bacterial toxins (leukocidin, alveolysin, and erythrogenic toxin A): generation of interleukin-8.

We analyzed the transcription and release of interleukin-8 (IL-8) from human polymorphonuclear granulocytes (PMNs) and a lymphocyte-monocyte-basophil (LMB) cell population stimulated for different time periods (30 min to 16 h) with pore-forming bacterial toxins (Panton-Valentine leukocidin [Luk-PV] and alveolysin [Alv]) as well as with the erythrogenic toxin A (ETA) as a superantigen. At high toxin concentrations (500 ng/10(7) cells), Luk-PV and Alv led to a decreased IL-8 generation from LMBs within the first 30 min; with PMNs, a slight increase in IL-8 release was observed. Under these conditions, stimulation with ETA did not lead to an altered cellular IL-8 release. At lower concentrations (5 and 0.5 ng/10(7) cells), all three toxins led to a continuous increase (over 16 h) in IL-8 release and IL-8 mRNA expression of PMNs and LMBs. Preincubation of the cells with the protein tyrosine kinase inhibitors lavendustin A and tyrphostin 25 led to a reduction of the toxin-mediated effects on IL-8 release and IL-8 mRNA expression when Luk-PV and Alv were used as stimuli. In contrast, IL-8 synthesis in cells which were stimulated with ETA was not influenced by protein tyrosine kinase inhibition. From our data, one may suggest that multiple pathways for IL-8 production are operative in human leukocytes.