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 erythrog enic toxin A (ETA) as a superantigen. At high toxin concentrations (50 0 ng/10(7) cells), Luk-PV and Alv led to a decreased IL-8 generation f rom LMBs within the first 30 min; with PMNs, a slight increase in IL-8 release was observed. Under these conditions, stimulation with ETA di d not lead to an altered cellular IL-8 release, At lower concentration s (5 and 0.5 ng/10(7) cells), all three toxins led to a continuous inc rease (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 inh ibitors lavendustin A and tyrphostin 25 led to a reduction of the toxi n-mediated effects on IL-8 release and IL-8 mRNA expression when Luk-P V and Alv were used as stimuli. In contrast, IL-8 synthesis in cells w hich were stimulated with ETA was not influenced by protein tyrosine k inase inhibition. From our data, one may suggest that multiple pathway s for IL-8 production are operative in human leukocytes.