Activation of alpha-human tumour necrosis factor (TNF-α) by human monocytes (THP-1) exposed to 2-chloroethyl ethyl sulphide (H-MG)

Abstract

Tumour necrosis factor (TNF) is a monokine produced by monocytes and macrophages in response to different stim uli. To determine whether vesicant agents such as half- mustard gas (H-MG; chemical structure: ClCH2CH 2SCH2CH3) may induce the release of TNF-α in human monocytes (THP-1), ELISA experiments were con ducted at different post exposure times. The results indi cate that: (1) Significant increases in the TNF-α (pg mL-1) concentration were observed as a function of time when THP-1 cells were exposed to 100 μL of 2 M H-MG. A spe cific serine-type protease inhibitor, Nα-p-tosyl-L-lysine chloromethyl ketone (TLCK), led to partial but significant inhibition of TNF activation. (2) Furthermore, this labora tory detected the generation of spin adducts of 2-methyl-2- nitrosopropane (MNP) having a resemblance to MNP adducts generated from hydrogen atom abstraction of pro tein constituents.1 The EPR/Spin Trapping data indicate the trapping of by-products of protein degradation after exposure to H-MG. TNF-α may play a role as a biochemi cal marker for pathophysiological changes induced by H- MG or related agents.