Heterogeneous pathways of oxidizing radical production in human neutrophils and the HL-60 cell line

Oxygen-derived free radicals with hydroxyl radical (OH.)-like reactivity are products of the human neutrophil respiratory burst. Such radicals, although dependent on O2-generation arise from complex oxidation reactions that may be independent of an iron-or lactoferrin-catalyzed Haber-Weiss mechanism. Differentiated HL-60 promyelocytic leukemia cells completely deficient in lactoferrin generate oxidizing radicals at a rate greater than that of human neutrophils, indicating lactoferrin-independent pathways for OH. generation. The further heterogeneity of pathways generating OH. activity in neutrophils is indicated by the cell concentration dependence of the reaction, the variability of H2O2 as a precursor reactant, and the various proportions of oxidizing radical activity to O2-detected in human neutrophils stimulated to a variety of agonists. The ethylene assay for oxidizing radical activity may detect different classes of oxidizing species capable of reacting with the aldehyde substrate. The complexity of defining the oxygen-derived radicals of the ethylene assay suggests methodologic difficulties of either quantitating or precisely defining the radicals generated in the respiratory burst by this method.