Activation of alpha-human tumour necrosis factor (TNF-alpha) by human monocytes (THP-1) exposed to 2-chloroethyl ethyl sulphide (H-MG).
Tumour necrosis factor (TNF) is a monokine produced by monocytes and macrophages in response to different stimuli. To determine whether vesicant agents such as half-mustard gas (H-MG; chemical structure: ClCH2CH2SCH2CH3) 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-alpha (pg mL-1) concentration were observed as a function of time when THP-1 cells were exposed to 100 microL of 2 M H-MG. A specific serine-type protease inhibitor, N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), led to partial but significant inhibition of TNF activation. (2) Furthermore, this laboratory detected the generation of spin adducts of 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 protein degradation after exposure to H-MG. TNF-alpha may play a role as a biochemical marker for pathophysiological changes induced by H-MG or related agents.
Arroyo
C M
CM
US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
Von Tersch
R L
RL
Broomfield
C A
CA
D002460:Cell Line; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000187:drug effects*
D005609:Free Radicals; D014409:Tumor Necrosis Factor-alpha; C031278:2-chloroethyl ethyl sulfide; D009151:Mustard Gas