Characteristics of formation and further metabolism of leukotrienes in the chopped human lung.
The bronchoconstrictive leukotrienes (LTs) LTC4, LTD4 and LTE4 (cysteinyl-LTs) and the chemoattractant LTB4 were formed in chopped human lung stimulated by the calcium ionophore A23187, or supplied with the precursor LTA4. In contrast, challenge with anti-IgE exclusively induced release of cysteinyl-LTs, indicating that LTB4 is not released as a primary consequence of IgE-mediated reactions in the human lung. Furthermore, several differences were observed with respect to formation and further conversion of LTB4 and LTC4 in the chopped lung preparation. Thus, exogenous [1-14C]arachidonic acid was dose-dependently converted to radioactive LTB4, whereas the cysteinyl-LTs released were not radiolabeled and the amounts of LTC4, D4 and E4 were not influenced by addition of increasing concentrations of arachidonic acid. LTC4 was rapidly and completely converted into LTD4 and LTE4, with no further catabolism of LTE4 within 90 min. The metabolism of LTB4 was much slower than that of LTC4. Thus, following a 60 min incubation approx. 25% of the material remained as LTB4, whereas 35% was omega-oxidized and 40% eluted on RP-HPLC as two unidentified peaks.
Kumlin
M
M
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Dahlén
S E
SE
D000888:Antibodies, Anti-Idiotypic; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007073:Immunoglobulin E; D007700:Kinetics; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000378:metabolism; D017999:Leukotriene E4; D015289:Leukotrienes / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D013189:SRS-A / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D001095:Arachidonic Acids; D015289:Leukotrienes; D013189:SRS-A; D007975:Leukotriene B4; D007073:Immunoglobulin E; D000001:Calcimycin; D017999:Leukotriene E4