952 A NEW GENETIC DISORDER OF NEUTROPHIL OXIDATIVE METABOLISM

Investigations of neutrophil function in a 7 y/o M with recurrent Pseudomonas cepacia pneumonia demonstrated Impaired intracelluar killing of catalase - positive bacteria; other functions including directed migration, phagocytosis, adherence & secretion (1° & 2° granule) were normal. Quantitative NBT reduction and chemiluminesence (CL) evolution by patient neutrophils (PN) were profoundly diminished (0.1-9% of normal) in response to soluble stimulants (PMA, A23187, NaF) (p<.001 to each), but were in a low normal range (31-77% nl) during phagocytosis or during adherence to plastic substrates. Similarly, superoxlde (O2−) generation and hexose monophosphate shunt activity of PN were profoundly diminished (0-3% nl) in response to soluble stimulants (p<.001), but demonstrated low normal activities (25-51% nl) during particle ingestlon. Maternal neutrophils (MN) demonstrated intermediate abnormalities of NBT reduction, CL evolution and O2− generation in response to soluble stimulants, but responses during phagocytosis were normal. Further studies to determine the mechanism of impaired oxldatlve activity showed elevated levels of cytochrome b245 on the surface of MN (470% nl), those of a half brother (550% nl) & PN (200% nl). However, during recovery from Pseudomonas cepacia pneumonia, cytochrome b245 was undetectable on PN. These findings indicate that defective oxidative metabolic activity in this disorder is related to abnormal regulation of cytochrome b245 expression on the neutrophil surface.