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Oxidative transformations of arachidonic acid in human dispersed lung cells: disparity between the utilization of endogenous and exogenous substrate
Author(s) -
Harvey J.,
Holgate S.T.,
Peters B.J.,
Robinson C.,
Walker J.R.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb08911.x
Subject(s) - arachidonic acid , chemistry , leukotriene c4 , ionophore , endogeny , leukotriene , thromboxane b2 , biochemistry , hydroxyeicosatetraenoic acid , stimulation , eicosanoid , prostaglandin , thromboxane , endocrinology , biology , platelet , enzyme , immunology , membrane , asthma
1 Eicosanoid release from human dispersed lung cells (HDLC) containing ca 5% mast cells was studied before and after cell activation with ionophore A23187 or anti‐IgE. 2 Basal release of eicosanoids synthesized from endogenous arachidonate was measured by radioimmunoassy. In descending order of abundance the products were: 5‐hydroxyeicosatetraenoic acid (5‐HETE) > thromboxane B 2 (TXB 2 ) > prostaglandin F 2α (PGF 2α ) ∼ immunoreactive (i)‐PGE 2 > PGD 2 > 6‐keto‐PGF 1α ∼ i‐LTC 4 . 3 Stimulation of HDLC with ionophore A23187 or, after passive sensitization, with anti‐IgE resulted in 2–10 fold increases in the generation of individual eicosanoids. In terms of net generation the most abundant products were PGD 2 and TXB 2 with either stimulus. Activation with A23187 caused net release of i‐LTC 4 and 5‐HETE, but these products were not measured after immunological activation. 4 A more complete profile of lipoxygenase products released from HDLC dispersed from one lung was obtained after separation by high performance liquid chromatography combined with ultra violet spectroscopy and bioassay. The major products released from the cells from this lung with ionophore stimulation were 13‐hydroxylinoleic acid > LTB 4 > 5‐HETE > 12‐HETE > LTC 4 > 15‐HETE > 11‐HETE ∼ 9‐HETE. 5 When the utilization of exogenous [ 14 C]‐arachidonic acid for prostanoid biosynthesis was compared to that of endogenous unlabelled arachidonate the formation of TXB 2 was consistently underestimated. These results imply compartmentalization of arachidonic acid utilization in Ca 2+ ‐activated HDLC. 6 In unstimulated cells the proportional formation of PGD 2 was overestimated when exogenous arachidonic acid was substrate. After activation with A23187 the proportions of PGD 2 were similar with both substrate sources. 7 The large proportions of PGD 2 and TXB 2 generated by HDLC further supports the view that these eicosanoids may be important inflammatory mediators in lung tissue.