The effect of leukotrienes on porcine alveolar macrophage function.
The ability of the synthetic leukotrienes LTB4, LTC4, LTD4 and LTE4 to stimulate porcine AM was compared with that of two known AM stimuli: zymosan, a particulate stimulus and phorbol myristate acetate (PMA), a soluble stimulus. The criteria for AM stimulation were: increased generation of superoxide anion (O2-), the release of the lysosomal enzymes N-acetyl-beta-D-glucosaminidase (NABG) and arylsulfatase and an increase in surface free energy. Whereas zymosan and PMA both stimulated AM according to each of the three criteria, the effect of leukotrienes was relatively minor. LTB4 (10(-6) M) and LTD4 (10(-6) M) caused a modest reduction in spontaneous O2- release by AM. LTD4 (10(-6) M) also caused a small (18%), but significant (p less than 0.05), reduction in the additional O2- release induced by PMA. LTC4 and LTE4 did not alter spontaneous O2- release. Neither spontaneous nor stimulated enzyme release was systematically altered by any of the leukotrienes. LTD4 caused a cysteine-inhibitable, dose-dependent increase in surface free energy with a plateau at concentrations above 10(-8) M. The increased surface free energy induced by LTD4 may be a consequence of binding to a surface dipeptidase.
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism; D007975:Leukotriene B4 / Q000494:pharmacology*; D017999:Leukotriene E4; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D011650:Pulmonary Alveoli / Q000166:cytology*; D013189:SRS-A / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D013189:SRS-A; D013481:Superoxides; D007975:Leukotriene B4; C016658:phorbolol myristate acetate; D017999:Leukotriene E4; D015054:Zymosan; D001192:Arylsulfatases; D000118:Acetylglucosaminidase; D013755:Tetradecanoylphorbol Acetate