Aberrant [correction of Abberant] cytosolic calcium ion mobilization in chronic granulomatous disease neutrophils.
Beside the inability to produce superoxide ions, neutrophils (PMN) from chronic granulomatous disease (CGD) patients show other functional defects, e.g. abnormal membrane potential reactions. We observed that PMN from a female CGD carrier, with a discrete mutation in one allele of the pg91(phox) gene and exhibiting extreme lyonization, showed a consistently and remarkably delayed PMN cytosolic calcium response to the tripeptide fMLP or leukotriene B4 (LTB4). In keeping with results from other CGD patients, membrane potential changes were abnormal, whereas chemotaxis and adherence was normal. Since phospholipase D-generated metabolites are important for calcium transients we examined the generation of phosphatidic acid, but found that to be normal. A male CGD patient with pg91(phox) deficiency exhibited a trend toward prolongation of this calcium response, whereas two other CGD patients (one with p47 and one with 67(phox) deficiencies) had normal calcium transients. Thus, our finding points to a defect of the stimulus response coupling for fMLP and LTB4, which is supposed to be characteristic for this patient or a subset of CGD patients.
Palmblad
Jan
J
The Center for Inflammation and Hematology Research, Department of Hematology, Karolinska University Hospital, Huddinge, Sweden. jan.palmblad@medhs.ki.se
Hansson
Anders
A
Heimbürger
Mikael
M
Ahlin
Anders
A
D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D009154:Mutation; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology