DEFICIENCY OF P67(PHOX), P47(PHOX) OR GP91(PHOX) IN CHRONIC GRANULOMATOUS-DISEASE DOES NOT IMPAIR LEUKOCYTE CHEMOTAXIS OR MOTILITY

Chronic granulomatous disease (CGD) is a syndrome characterized by fai lure of the NADPH oxidase of phagocytes that generates superoxide, whi ch is central to the microbicidal process. Cytosolic components of thi s oxidase system include the proteins p67(phox) and p47(phox), deficie ncies of which cause the autosomal recessive form of CGD, whereas the X-linked form of the disease is characterized by a deficiency in the p lasma membrane component gp91(phox). Components of the oxidase system have been reported to be associated with the cytoskeleton and neutroph ils from CGD patients have been reported to have a defective chemotact ic response in Boyden chambers. Using a chamber that permits the direc t observation of cell behaviour in a linear gradient of a chemoattract ant, we have analysed the chemotactic response of neutrophils from a p atient lacking p67(phox); from another lacking p47(phox) and from a th ird lacking gp9l(phox). The results of measuring the speeds and direct ions of locomotion of the cells show that their speeds are undiminishe d relative to cells from healthy control subjects and that their direc tions of migration are at least as strongly biased in the direction of the gradient as those of the control cells. We conclude that these de finitive aspects of the chemotactic response are not abnormal in eithe r the autosomal recessive or the X-linked forms of CGD and that they a re therefore not factors in the predisposition to infection that chara cterizes the syndrome.