The regulation of human eosinophil function by endogenous mono-hydroxy-eicosatetraenoic acids (HETEs)
Goetzl, E.J.; Weller, P.F.; Sun, F.F.
Journal of Immunology 124(2): 926-933
1980
ISSN/ISBN: 0022-1767 PMID: 7356719 Document Number: 158474
The possibility that endogenous mono-hydroxy-eicosatetraenoic acids (HETE) derived from the lipoxygenation of arachidonic acid might influence functions of human eosinophils from hypereosinophilic subjects was examined by analyzing activities of the purified HETE and effects of depletion of intracellular HETE on eosinophil migration. Incubation of arachidonic acid with the 17,000 .times. g supernatant from homogenates of human eosinophils generated predomiantly 11-HETE, 9-HETE, and 5-HETE. The same mono-HETE and 5,12-di-HETE were the major products extracted from intact eosinophils. The ratio of the quantity of 9-HETE to that of 8-HETE generated by eosinophil homogenates and recovered from intact eosinophils exceeded 6, as contrasted with 0.75 for human neutrophils, whereas the eosinophil content of 5-HETE was less than that of the human neutrophil. Incubation of eosinophils with the calcium ionophore A23187 or with chemotactic fragments of C5 G-Fc receptors or the release of the eosinophil enzymes .beta.-glucuronidase and arylsulfatase B. Preincubation of eosinophils with the lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid (TYA) at a concentration of 10 .mu.M or nordihydroguaiaretic acid (NDGA) at a concentration of 5 .mu.M depleted the unstimulated eosinophil content of HETE by 41-60% and the C5fr-stimulated eosinophil content of HETE by 65-83%, and concomitantly inhibited random migration and chemotaxis to a significant extent. Addition of purified native HETE to the HETE-depleted eosinophils restored migration to normal levels. The most potent principle in reversing inhibition was the 5-HETE. The HETE generated by eosinophils potentially may fulfill a role as endogenous cellular mediators as well as exhibiting the capacity to evoke inflammatory responses.