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These studies evaluated further the relationship between the metabolism of reactive oxygen species (ROS) and prostaglandins in human granulocytes. Our experiments examined (1) the effects of several scavengers of ROS on thromboxane B2 (TXB2) production by zymosan-stimulated PMNs, (2) the capacity of the granulocytes of patients with chronic granulomatous disease (CGD) to produce TXB2, and finally (3) the generation of oxygen radicals in PMNs stimulated to produce TXB2 by the enzyme phospholipase A2. Our results confirm that both zymosan- and PMA-stimulated PMNs release increased amounts of TXB2. This enhanced production of TXB2 by normal PMNs could not be impaired and, in fact, appeared to be enhanced by scavengers of ROS. The PMNs of one patient with CGD produced TXB2 in an amount similar to those of healthy persons, whereas the TXB2 produced by the PMNs of a second patient was markedly increased. Finally, the enzyme phospholipase A2 stimulated TXB2 production in PMNs without stimulating the production of ROS. These data indicate that the activation of prostaglandin metabolism in PMNs is not dependent on the simultaneous production of ROS by these cells. However, the simultaneous production of ROS may be associated with an alteration prostaglandin metabolism.
Abbreviations:(ROS) (reactive oxygen species), (TXB2) (thromboxane B2), (TXA2) (thromboxane A2), (CDG) (chronic granulomatous disease), (PMN) (polymorphonuclear leukocyte), (OH·) (), hydroxyl radical (), (O2−) (superoxide), (DPBS) (Dulbecco's phosphate-buffered saline), (DMSO) (dimethyl sulfoxide), (PMA) (phorbol myristate acetate), (PGH2) (prostaglandin H2), (PGF) (prostaglandin F)
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Accepted: July 12, 1983
Received: June 17, 1983
☆The results were presented at the meeting of AFCR in Chicago, November 1981; at the American Society of Hematology, San Antonio, December 1981; and published in abstract form (Clin Res 29:720, 1981).
☆☆This work was supported by grants from the NCI, No. CA 32321-01, and Central Ohio Heart Association.
© 1983 Published by Elsevier Inc.