Deficiency of p67phox, p47phox or gp91phox in chronic granulomatous disease does not impair leucocyte chemotaxis or motility.
Chronic granulomatous disease (CGD) is a syndrome characterized by failure of the NADPH oxidase of phagocytes that generates superoxide, which is central to the microbicidal process. Cytosolic components of this oxidase system include the proteins p67phox and p47phox, deficiencies of which cause the autosomal recessive form of CGD, whereas the X-linked form of the disease is characterized by a deficiency in the plasma membrane component gp91phox. Components of the oxidase system have been reported to be associated with the cytoskeleton and neutrophils from CGD patients have been reported to have a defective chemotactic response in Boyden chambers. Using a chamber that permits the direct observation of cell behaviour in a linear gradient of a chemoattractant, we have analysed the chemotactic response of neutrophils from a patient lacking p67phox; from another lacking p47phox and from a third lacking gp91phox. The results of measuring the speeds and directions of locomotion of the cells show that their speeds are undiminished relative to cells from healthy control subjects and that their directions of migration are at least as strongly biased in the direction of the gradient as those of the control cells. We conclude that these definitive aspects of the chemotactic response are not abnormal in either the autosomal recessive or the X-linked forms of CGD and that they are therefore not factors in the predisposition to infection that characterizes the syndrome.
Zicha
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MRC Muscle and Cell Motility Unit, The Randall Institute, King's College London.
Dunn
G A
GA
Segal
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AW
D000328:Adult; D015153:Blotting, Western; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009504:Neutrophils / Q000502:physiology*; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics
D008562:Membrane Glycoproteins; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D009240:N-Formylmethionine Leucyl-Phenylalanine; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1