IL-8 enhances antibody-dependent cellular cytotoxicity in human neutrophils.
Human neutrophils are able to kill in vitro colorectal carcinoma cell line SW11-16 coated with mAb 17-1A, but they are not cytotoxic towards a non-immunized tumour target. Neutrophil exposure to the inflammatory cytokine, IL-8, produces a significant increase in antibody-dependent cellular cytotoxicity, which is related to IL-8 concentration. Oxyradical production is one of the lytic mechanisms used by phagocytes, and IL-8 is shown to activate this function, which does not occur if neutrophils are pretreated with the protein kinase C inhibitor, staurosporine, but is increased by R59022, a dyacylglycerol kinase inhibitor. The IL-8 effect is mediated by protein kinase C, which is potentiated by the calcium flux induced by the interaction between antibody coating tumour target and Fc gamma RIII on effector cells, as previously demonstrated. Data suggest a possible new role for IL-8 in tumour surveillance.
Reali
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Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi, Ferrara, Italy.
Spisani
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S
Gavioli
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R
Lanza
F
F
Moretti
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S
Traniello
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D000838:Anions / Q000378:metabolism; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D019852:Diacylglycerol Kinase; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011744:Pyrimidinones / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology; D019311:Staurosporine; D013481:Superoxides / Q000737:chemistry; D013844:Thiazoles / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000470:Alkaloids; D000838:Anions; D016209:Interleukin-8; D011744:Pyrimidinones; D013844:Thiazoles; D013481:Superoxides; C047505:R 59022; D017853:Phosphotransferases (Alcohol Group Acceptor); D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D019311:Staurosporine