Augmentative effects of tumor necrosis factor-alpha (human, natural type) on polymorphonuclear leukocyte-derived superoxide generation induced by various stimulants.
We investigated the effects of tumor necrosis factor-alpha (human, natural type: n-TNF) on polymorphonuclear leukocyte (PMN)-derived superoxide generation by the new method of Cypridina luciferin analog-dependent chemiluminescence, which had high sensitivity and specificity to superoxide. Preincubation of PMNs with n-TNF for 3 min increased PMN-derived superoxide generation induced by phorbol myristate acetate, A23187, opsonized zymosan and N-formyl-methionyl-leucyl-phenylalanine in a concentration dependent manner (0.5-50 Japan reference units/ml of n-TNF). In addition, the enhanced PMN-derived superoxide generation by n-TNF showed a positive correlation to the preincubation time of PMNs with n-TNF (3-15 min). However, a direct incubation of PMNs with n-TNF for 1 h did not induce superoxide from PMNs without the above stimulants. The augmentative effects of n-TNF on PMN-derived superoxide generation should be useful in the PMN-mediated host defense mechanism, such as bactericidal and antitumor activity. The local concentration of n-TNF and the n-TNF-PMN contact time are considered very important in obtaining these effects more efficiently in addition to the presence of PMN-stimulants including complements, chemotactic peptides and phorbol esters.
Yoshikawa
T
T
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Takano
H
H
Naito
Y
Y
Oyamada
H
H
Ueda
S
S
Kondo
M
M
D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000502:physiology; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011493:Protein Kinase C