STIMULUS SPECIFICITY OF PROSTAGLANDIN INHIBITION OF RABBIT POLYMORPHONUCLEAR LEUKOCYTE LYSOSOMAL-ENZYME RELEASE AND SUPEROXIDE ANION PRODUCTION

  • 1 January 1984
    • journal article
    • research article
    • Vol. 115  (1) , 9-16
Abstract
Prostaglandins (PG) of the E series and PGI2 have inhibited acute inflammatory reactions in vivo and polymorphonuclear leukocyte (PMN), chemotaxis, lysosomal enzyme release, and superoxide anion (O2-) production in vitro. This inhibition of neutrophil stimulation by PGE and PGI2 has been correlated with their ability to increase intracellular cAMP levels. The mechanism(s) by which PGE and PGI2 alter the complex biochemical and biophysical events associated with stimulus-response coupling in the neutrophil are not clear. Both PGE and PGI2 in micromolar concentrations inhibited formyl-methionyl-leucyl-phenylalanine (FMLP)- and zymosan-induced lysosomal enzyme secretion and superoxide anion production in a dose-dependent manner. No preincubation time of PMN with the PG was required for inhibition. Addition of PGE 10 s or later after FMLP stimulation did not alter the biologic response of the neutrophils to the stimulus, suggesting that the PG inhibition effects early events associated with stimulus-response coupling in the neutrophil. PG inhibition of lysosomal enzyme release by the Ca ionophore [calcimycin] A23187 was overcome by increasing the extracellular ionophore and/or Ca concentration, suggesting that PG may modulate intracellular free Ca levels in a manner similar to that observed with platelets. Inhibition of phorbol myristate acetate (PMA)-induced neutrophil lysosomal enzyme secretion by PGE and PGI2 was overcome by increasing concentrations of PMA. Neither PGE or PGI2 altered O2- production by PMA-treated neutrophils. A dissociation between PMA-stimulated O2- production and lysosomal enzyme release is indicated. Inhibition of neutrophil stimulation by PGE and PGI2 apparently is a result of increased intracellular cAMP levels and modulation of Ca-dependent events. There apparently are at least 2 mechanisms by which PMN can be stimulated to produce O2- 1 inhibited by PGE and PGI2 and a 2nd independent of PG modulation.

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