Lipopolysaccharide primes human alveolar macrophages for enhanced release of superoxide anion and leukotriene B4: self-limitations of the priming response with protein synthesis.
Human alveolar macrophages (AM) can produce potent reactive oxygen intermediates (ROI) and arachidonic acid metabolites (eicosanoids), which have important roles in host defense and the pathogenesis of some diseases of the lung. Bacterial lipopolysaccharide (LPS) is believed to cause profound lung injury and can prime mouse peritoneal macrophages for the enhanced secretion of ROI and eicosanoids. Therefore, we investigated the effect of LPS pretreatment on the ability of AM to release superoxide anions (O2-) and leukotriene B4 (LTB4). LPS can prime AM for the enhanced secretion of O2- and LTB4, regardless of whether they are derived from nonsmokers or smokers. Moreover, judging from the time-response characteristics, this priming for LTB4 release could be inhibited in the later stages of pretreatment, when the O2(-)-releasing capacity was enhanced. The priming inhibition was prevented, at least in part, by cycloheximide, but not by SOD and/or catalase. In addition, cycloheximide also inhibited the priming for O2- release. Hence, protein synthesis might be necessary for the priming for O2- release and for inhibiting the priming for LTB4 release. This phenomenon of self-limiting the priming response with LPS seems to be very important when we consider the high oxygen tension in the lungs and the many bacterial substances inspired into alveoli.
Department of Infection and Inflammation, Kyoto University, Japan.
K
K
Suzuki
T
T
Yamamoto
A
A
Sato
T
T
Murayama
R
R
Amitani
K
K
Yamamoto
F
F
Kuze
D000328:Adult; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002851:Chromatography, High Pressure Liquid; D017077:Culture Media, Conditioned; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D014176:Protein Biosynthesis; D012907:Smoking / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D013481:Superoxides; D007975:Leukotriene B4; D003513:Cycloheximide; D013482:Superoxide Dismutase