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Leukotriene B 4 metabolism in neutrophils of patients with chronic granulomatous disease: phorbol myristate acetate decreases endogenous leukotriene B 4 via NADPH oxidase‐dependent mechanism
Author(s) -
HAMASAKI T.,
SAKANO T.,
KOBAYASHI M.,
SAKURA N.,
UEDA K.,
USUI T.
Publication year - 1989
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1989.tb00249.x
Subject(s) - endogeny , chronic granulomatous disease , nadph oxidase , chemistry , leukotriene , phorbol , leukotriene b4 , intracellular , leukotriene c4 , reactive oxygen species , arachidonic acid , oxidase test , biochemistry , protein kinase c , enzyme , immunology , biology , inflammation , asthma
. We studied the effect of phorbol myristate acetate (PMA) on endogenous leukotriene B 4 (LTB 4 ) metabolism of calcium ionophore A23187‐stimulated human neutrophils. Preincubation of normal neutrophils with PMA significantly suppressed the recovery of endogenous LTB 4 induced by A23187. PMA did not suppress the recovery of LTB 4 produced by neutrophils from patients with chronic granulomatous disease (CGD), which is known to be defective in NADPH oxidase activation to produce reactive oxygen species (ROS). PMA inhibited the formation of ω‐oxidation products of LTB 4 , but enhanced arachidonic acid release in normal and CGD neutrophils. Furthermore, 5‐lipoxygenase activity of 10000 times g supernatants from normal neutrophils pretreated with PMA was equivalent to that of the controls. Decrease in LTB 4 recovery was not attributed to the suppression of the intracellular Ca 2+ increase. Thus, it is suggested that reactive oxygen species (ROS) produced by PMA may directly affect endogenous LTB 4 and convert it into metabolite(s) distinct from ω‐oxidation products.