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 TNFα (rTNFα) 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, rTNFα, in a dose-dependent manner, primed neutrophils for HOCl production in response to the weak agent unopsonized zymosan. rTNFα concentrations as low as 10 U/ml resulted in a fivefold increase in HOCl in this system. rTNFα-primed cells also exhibited increased phagocytosis. Priming in this model system occurred regardless of whether cells were preincubated with rTNFα before addition of zymosan or coincubated with both rTNFα and zymosan. rTNFα priming for HCOl production could not be washed away and required a lag period of ~ 10 min. rTNFα priming was not dependent on extracellular Ca²⁺ and Mg²⁺. Preincubation experiments demonstrated that rTNFα priming was not inhibited by the microfilament blocker cytochalasin B. Although the mechanism remains unclear, these findings demonstrate that rTNFα has an important priming effect on the neutrophil myeloperoxidase pathway.