Tumor necrosis factor primes neutrophils for hypochlorous acid production
She, Z.W.; Wewers, M.D.; Herzyk, D.J.; Sagone, A.L.; Davis, W.B.
American Journal of Physiology 257(6 Pt 1): L338-L345
1989
ISSN/ISBN: 0002-9513 PMID: 2558582 Document Number: 329220
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 .apprx. 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.