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.
König
B
B
Lehrstuhl für Medizinische Mikrobiologie und Immunologie, AG Infektabwehrmechanismen, Ruhr-Universität Bochum, Germany.
Köller
M
M
Prevost
G
G
Piemont
Y
Y
Alouf
J E
JE
Schreiner
A
A
König
W
W
D001426:Bacterial Proteins; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D005098:Exotoxins / Q000276:immunology*; D006460:Hemolysin Proteins / Q000276:immunology*; D006461:Hemolysis; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007956:Leukocidins / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D009570:Nitriles / Q000494:pharmacology; D009930:Organic Chemicals; D010636:Phenols / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D020032:Tyrphostins
D001426:Bacterial Proteins; D017931:DNA Primers; D005098:Exotoxins; D006460:Hemolysin Proteins; D016209:Interleukin-8; D007956:Leukocidins; D008565:Membrane Proteins; D009570:Nitriles; D009930:Organic Chemicals; D010636:Phenols; C117980:SpeA protein, Streptococcus pyogenes; D020032:Tyrphostins; C027951:erythrogenic toxin; C079836:tyrphostin 25; C062898:lavendustin A; C014963:alveolysin; D011505:Protein-Tyrosine Kinases