Activated rat neutrophils. Correlation of arachidonate products with enzyme secretion but not with O(2)- generation

Functional responses (enzyme secretion and generation of O2-) have been studied in rat neutrophils with the use of a variety of different agonists which vary in their ability to activate neutrophils. Concomitantly, the authors have analyzed the cells for production of cyclooxygenase (PGE2, PGF2 alpha, and TXB2) and lipoxygenase (monoHETEs and LTB4) products in order to determine whether there is a correlation between functional responses and arachidonate products in stimulated neutrophils. The studies indicate that enzyme secretion is closely correlated with generation of arachidonate (cyclooxygenase as well as lipoxygenase) products. These responses are dependent on the dose of agonist employed, but there does not appear to be a unique pattern of arachidonate products that can be attributed to a specific agonist. With respect to monohydroxyeicosatetraenoic acid (monoHETE) generation, we demonstrate that stimulated rat neutrophils selectively produce 5-HETE, to the virtual exclusion of 12-HETE and 15-HETE. The production of O2- from stimulated rat neutrophils is correlated neither with enzyme secretion nor with the generation of arachidonate products. These studies suggest that enzyme secretion and O2- generation are mediated by two fundamentally different intracellular pathways, even though these functional responses probably derive from common agonist-receptor interactions on the plasma membrane.