Enhancement of neutrophil response by SH-containing compounds: modulation of superoxide and hydrogen peroxide production.
Anti-inflammatory effects of SH compounds in vivo and their effects on lymphocytes and macrophages in vitro have been described, but little is known about the mechanism of action or their effects on the neutrophil. In the present study the activity of seven low molecular weight non-protein SH compounds was compared. At a concentration of 3 X 10(-4)M all the compounds enhanced the activity of the HMP shunt of zymosan-stimulated neutrophils by 26-48% and that of PMA-stimulated cells by 6-44% above the control value (14.2 nmol CO2/2.5 X 10(6) neutrophils/30 min). Pretreatment of neutrophils with SH compounds for 15 min resulted in enhanced release of O-.2 by stimulated neutrophils in all cases, with the exception of GSH, by up to 87% above that of control. These effects were largely related to the ability of the compounds to modulate the release of O-.2 and H2O2 by stimulated neutrophils when present in the reaction mixture. Only the compounds alpha-MPG and cysteine had a mild preserving effect on the intracellular GSH concentration of stimulated neutrophils. None of the compounds tested had any adverse effect on phagocytosis or killing of opsonized bacteria by the neutrophils. SH compounds may protect sensitive SH groups of functional proteins by providing an easily accessible source of oxidizable SH groups in times of high oxidative stress, and their ability to interact with oxygen products could in part explain their anti-inflammatory properties.
D001770:Blood Bactericidal Activity / Q000187:drug effects; D005978:Glutathione / Q000097:blood; D006600:Hexosephosphates / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood*; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013481:Superoxides / Q000097:blood*
D006600:Hexosephosphates; D013438:Sulfhydryl Compounds; D013481:Superoxides; D006861:Hydrogen Peroxide; D005978:Glutathione