Termination of the Respiratory Burst in Human Neutrophils

Abstract

A B S T R A C T Recent evidence has suggested that a particulate 02-forming system is responsible for the respiratory burst in activated neutrophils. The respiratory burst is normally a transient event, lasting only 30-60 min. To investigate the mechanism by which the btrst is terminated, we examined the 02-forming activity of neutrophil particles as a function of time in the presence and absence of agents known to affect the function of intact cells. Measurements of the°2-forming capacity of the particles against time of exposure of neutrophils to opsonized zymosan, a potent stimulating agent, revealed a rapid fall in activity when exposure was continued beyond 3 min. Exposure to zymosan under conditions in which the myeloperoxidase system was inactive (i.e., in the presence of myeloperoxidase inhibitors, or in the absence of oxygen) resulted in a substantial increase in the initial 02-forming activity of particles from the zymosan-treated cells, but did not prevent the sharp fall in activity seen when zymosan exposure exceeded 10 min. The fall in activity was, however, prevented when activation took place in the presence of cytochalasin B (1.5 ,ugml), an agent thought to act largely by paralyzing the neutrophil through an interaction with its microfilament network.We conclude from these findings that the termination of the respiratory burst results at least in part from the inactivation of the particulate 02-forming system. This inactivation involves at least two processes which probably act simultaneously. One is the destruction of the system through the action of myeloperoxidase. The other appears to require active cell motility and is independent of oxygen. The current view holds that the 02-forming system of the neutrophil is located in the plasma membrane. It may be that the second process involves the internalization and degradation of this membrane-bound system.

Increased atherosclerosis in myeloperoxidase-deficient mice

“…Ascorbate, a potent inhibitor of MPO-catalyzed chlorination, is an essential vitamin in humans, but not in mice (85). Human MPO-deficient neutrophils have been reported to have a prolonged respiratory burst (86). We failed to observe a significant difference in either duration or initial rate using our animal model.…”

Increased Activity of the Respiratory Burst in Cord Blood Neutrophils: Kinetics of the NADPH Oxidase Enzyme System in Subcellular Fractions

“…Evidence for the role of MPO in terminating the respiratory burst has been presented (31). Furthermore, activation of the respiratory burst may require translocation of cytochrome b and other constituents from specific granules to plasma membrane (32).…”

Chemotactic factor‐induced generation of superoxide radicals by human neutrophils

“…However, the lack of enhancement by antimycin A, another respiratory chain inhibitor, suggests that cyanide ion's effect on respiration is not responsible for the enhancement of superoxide production. Cyanide is also a general heme-enzyme inhibitor and its enhancement of superoxide generation might be explained by an effect on myeloperoxidase (25). Indeed, cyanide, azide, and methimazole, at concentrations ( 10-4M) that inhibit myeloperoxidase activity in vitro have been shown to augment superoxide production by human neutrophils phagocytizing opsonized zymosan particles (25).…”