Tumor necrosis factor primes neutrophils for hypochlorous acid production.
Tumor necrosis factor (TNF) has a weak direct effect on neutrophil oxidative metabolism and primes neutrophils for oxidant release in response to other stimuli. We examined the effect of recombinant human TNF alpha (rTNF alpha) on production of hypochlorous acid (HOCl) by human neutrophils. TNF alone, even at concentrations of 1,000 U/ml, did not stimulate HOCl production. In contrast, rTNF alpha, in a dose-dependent manner, primed neutrophils for HOCl production in response to the weak agent unopsonized zymosan. rTNF alpha concentrations as low as 10 U/ml resulted in a fivefold increase in HOCl in this system. rTNF alpha-primed cells also exhibited increased phagocytosis. Priming in this model system occurred regardless of whether cells were preincubated with rTNF alpha before addition of zymosan or coincubated with both rTNF alpha and zymosan. rTNF alpha priming for HOCl production could not be washed away and required a lag period of approximately 10 min. rTNF alpha priming was not dependent on extracellular Ca2+ and Mg2+. Preincubation experiments demonstrated that rTNF alpha priming was not inhibited by the microfilament blocker cytochalasin B. Although the mechanism remains unclear, these findings demonstrate that rTNF alpha has an important priming effect on the neutrophil myeloperoxidase pathway.
She
Z W
ZW
Division of Pulmonary and Critical Care, Ohio State University, Columbus 43210.
Wewers
M D
MD
Herzyk
D J
DJ
Sagone
A L
AL
Davis
W B
WB
D002118:Calcium / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D006997:Hypochlorous Acid / Q000097:blood*; D066298:In Vitro Techniques; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003571:Cytochalasin B; D006997:Hypochlorous Acid; D015054:Zymosan; D004492:Edetic Acid; D008274:Magnesium; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium