Diminished production of prostaglandin E2 by monocytes of newborns is due to altered fatty acid membrane content and reduced cyclooxygenase activity.
To determine the biochemical basis for reduced PGE2 expression by cord blood monocytes relative to adult peripheral blood monocytes, fatty acid composition of cell membranes together with the amount and activity of enzymes involved in the cyclooxygenase pathway were investigated. Gas chromatographic analysis of mononuclear cell fatty acids showed a significant reduction in long chain fatty acids, including arachidonic acid. Acylase and phospholipase A2 activity, together with lipocortin 1 levels, were similar in cord and adult monocytes. No difference in amounts of the 70-kDa cyclooxygenase type 1 enzyme was observed between the monocyte sources. The 74k-Da cyclooxygenase type 2 enzyme was synthesized de novo upon LPS stimulation in comparable amounts in both cord and adult monocytes, with both monocyte types responding with equal sensitivity to LPS. The ability of microsomes, prepared from cord monocytes, to convert arachidonic acid into eicosanoids of the cyclooxygenase pathway was reduced. In contrast, the ability of acetylated microsomes to convert PGG2 to PGE2 was comparable, suggesting that the deficiency in PGE2 production by cord monocytes is due to reduced activity, specifically at the cyclooxygenase-active site rather than the peroxidase active site. In conclusion, it appears that both reduced fatty acid content and diminished cyclooxygenase activity are responsible for diminished eicosanoid production by cord monocytes.
Murphy
F J
FJ
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Reen
D J
DJ
D000107:Acetylation; D000328:Adult; D000581:Amidohydrolases / Q000378:metabolism; D017305:Annexin A1 / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis* / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D009000:Monocytes / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D017305:Annexin A1; D001095:Arachidonic Acids; D005227:Fatty Acids; D007527:Isoenzymes; D008563:Membrane Lipids; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D000581:Amidohydrolases; C019665:amidase; D015232:Dinoprostone