Chemotactic deactivation of human neutrophils: role of stimulation of hexose monophosphate shunt activity in nonspecific deactivation.

We have investigated the mechanism of the nonspecific component of chemotactic deactivation of human neutrophils. This component of deactivation occurs on exposure of neutrophils to larger doses of cytotaxin and is expressed as depressed subsequent spontaneous migration and chemotaxis toward all cytotaxins tested. We demonstrate a possible mechanistic association between stimulation of hexose-monophosphate shunt activity and the nonspecific component of deactivation. This association is evidenced by failure to effect deactivation of 0 degrees C, by the ability of non-chemotactic stimulatory agents to mimic cytotaxin-induced deactivation, by the ability of agents which block shunt activity to protect against deactivation, and by the ability of methylene blue to deactivate neutrophils from individuals with chronic granulomatous disease. Thus, excessive stimulation of shunt activity, possibly through generation of products of oxygen metabolism, appears to have an inhibitory influence on nonspecific neutrophil migratory functions.