ACTIVATION OF ALPHA-HUMAN TUMOR-NECROSIS-FACTOR (TNF-ALPHA) BY HUMAN MONOCYTES (THP-1) EXPOSED TO 2-CHLOROETHYL ETHYL SULFIDE (H-MG)

Tumour necrosis factor (TNF) is a monokine produced by monocytes and m acrophages in response to different stimuli. To determine whether vesi cant agents such as half-mustard gas (H-MG; chemical structure: ClCH2C H2SCH2CH3) may induce the release of TNF-alpha in human monocytes (THP -1), ELISA experiments were conducted at different post exposure times . The results indicate that: (1) Significant increases in the TNF-alph a (pg mL(-1)) concentration were observed as a function of time when T HP-1 cells were exposed to 100 mu L of 2 M H-MG. A specific serine-typ e protease inhibitor, N-alpha-p-tosyl-L-lysine chloromethyl ketone (TL CK), led to partial but significant inhibition of TNF activation. (2) Furthermore, this laboratory detected the generation of spin adducts o f 2-methyl-2-nitrosopropane (MNP) having a resemblance to MNP-adducts generated from hydrogen atom abstraction of protein constituents.' The EPR/Spin Trapping data indicate the trapping of by-products of protei n degradation after exposure to H-MG. TNF-alpha may play a role as a b iochemical marker for pathophysiological changes induced by HMG or rel ated agents.