Leukotriene B4 Biosynthesis in Polymorphonuclear Leukocytes from Blood of Umbilical Cord, Infants, Children, and Adults

Abstract

ABSTRACT. The biosynthesis of 5(S), 12(R)-dihydroxy-6,14-cis-8,lO-trans-eicosatetraenoic acid, leukotriene B4, by human polymorphonuclear leukocytes was examined in relation to age. The leukotriene B4 production by polymorphonuclear leukocytes from unbilical cords, infants, and adults was assayed using high pressure liquid chromatography. The specificity of the leukotriene B4 assay was examined by gas chromatography mass spectrometry. Polymorphonuclear leukocytes from 10 umbilical cords, 24 infants and children, and 10 adults were examined for their ability to synthesize leukotriene B4, in vitro after stimulation by the ionophore A23187 or platelet-activating factor. Among the infants and children, there was a slight agedependent increase of leukotriene B4 production by polymorphonuclear leukocytes in response to ionophore A23187, but it was not statistically significant. Leukotriene B4 production by polymorphonuclear leukocytes in the umbilical cords and infants was not significantly lower than that of polymorphonuclear leukocytes in adults in response to both ionophore A23187 and platelet-activating factor under our experimental conditions. (Pediatr Res 20: 402-406,1986) Abbreviations PMN, polymorphonuclear leukocytes LTB4, leukotriene B4; 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid GC-MS, gas chromatography mass spectrometry PAF, platelet-activating factor fMLP, formyl-methionyl-leucyl-phenylalanine RP-HPLC, reversed phase high pressure liquid chromatography SP-HPLC, straight phase high pressure liquid chromatography RIA, radioimmunoassay SIM, selected ion monitoring 5S,12S-DHETE, 5(S),12(S)-dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid PGB, prostaglandin B2 [2H4]PGF2,, tetradeuterated prostaglandin Fza ME-DMiPS, methyl ester dimethylisopropylsilyl

Impaired Leukotriene B4 Release by Neonatal Polymorphonuclear Leukocytes

“…However, our data conflict only partially with those of Kikawa et al (24). Similar to their results, our findings provide evidence that in N-PMN the 5-lipoxygenase pathway for LTB, synthesis is fully developed at birth.…”

“…Even though GC-MS is the preferred method to assay LTB, and its metabolites in biologic samples, RIA offers important practical advantages over other assays (23). HPLC is the technique most frequently used for LTB, analysis; however, it shows a lower sensitivity and specificity than GC-MS and RIA (21,24).…”

Biochemical, Structural, and Functional Abnormalities of Polymorphonuclear Leukocytes in the Neonate

“…Since it is produced by PMNs upon stimulation with chemotactic factors such as C5, and FMLP, it may serve as an intra-or intercellular second messenger. However, Kikawa et al (73) …”

“…The reasons for this are currently not known. One possibility is related to the generation of LTB4 by the PMNs of neonates (73). This substance has potent PMN activating properties.…”