NEUTROPHIL MEMBRANE-POTENTIAL CHANGES AND HOMOTYPIC AGGREGATION KINETICS ARE PH-DEPENDENT - STUDIES OF CHRONIC GRANULOMATOUS-DISEASE

Activated polymorphonuclear neutrophil granulocytes (PMN) from patient s with chronic granulomatous disease (CGD) show reduced electron-proto n shifts and an inability to acidity the cell. We studied whether this impaired pH-regulating capacity affected PMN membrane potential chang es and the kinetics of homotypic aggregation by changing the extracell ular pH over a wide range. At pH 7.4 normal PMN showed a rapid, transi ent membrane depolarization to leukotriene B-4 (LTB(4)) and a slower r esponse to N-formyl-methionyl-leucyl-phenylalanine, In contrast, PMN f rom 13 patients with CGD exhibited no or minute depolarization to thes e stimuli and 77% of tested patients with CGD displayed absence or mar ked reductions of the disaggregation to LTB(4). On acidification to pH 5.0 to 6.4, PMN membrane depolarization appeared in six of nine teste d patients. Likewise, disaggregation became evident in all of three pa tients. On alkalinization of normal PMN to pH 8.0 to 9.0, membrane dep olarization and disaggregation to LTB(4) disappeared, and cells reacte d as CGD PMN. this change was not due to inefficient signal transducti on, because normal PMN enhanced the superoxide ion production to N-for myl-methionyl-leucyl-phenylalanine on this alkalinization. Cytosolic p H changes in resting and LTB(4)-activated CGD cells at ph 6.0, 7.4, an d 8.5 were similar those in control cells but for absence of an initia l acidification. Thus neutrophil membrane potential changes and aggreg ation kinetics to LTB(4) are abnormal in patients with CGD and return toward normal on extracellular acidification.