Normal levels of constitutive and death receptor-mediated apoptosis of peripheral blood neutrophils from patients with chronic idiopathic neutropenia.
To investigate the role of neutrophil apoptosis in the pathogenesis of chronic neutropenia, we examined constitutive and death receptor-mediated apoptosis ex vivo of peripheral blood neutrophils obtained from six chronic idiopathic neutropenia (CIN) patients and six healthy adult blood donors. Apoptosis was quantified based on phosphatidylserine externalization and caspase-3 activation in freshly isolated neutrophils or after overnight cultivation of neutrophils in the absence or presence of pro- or anti-apoptotic factors, including the pan-caspase inhibitor, zVAD-fmk. Neutrophils from CIN patients receiving treatment with granulocyte colony-stimulating factor appeared to be more prone to constitutive apoptosis than cells from untreated patients; however, further investigations in larger cohorts of patients are needed to validate these pilot studies. Overall, the level of neutrophil apoptosis was similar in patient and control groups, thus supporting the notion that the underlying defect in these neutropenia patients lies elsewhere, such as in the bone marrow microenvironment.
Garwicz
Daniel
D
Division of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden. Daniel.Garwicz@ki.se
Palmblad
Jan
J
Fadeel
Bengt
B
D000328:Adult; D000369:Aged, 80 and over; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D053218:Receptors, Death Domain / Q000097:blood / Q000502:physiology*
D053218:Receptors, Death Domain