Involvement of the beta2-integrin CD18 in apoptosis signal transduction in human neutrophils.
OBJECTIVE
To examine the hypothesis that an accelerated rate of neutrophil apoptosis occurs following beta2-integrin activation, and further investigate the signal transduction pathways involved.


METHODS
Human polymorphonuclear neutrophils.


METHODS
Neutrophils were challenged with pansorbins coated with antibodies towards the beta2-integrin subunit CD18 in a proportion of 1:100 with or without the inhibitors diphenylene iodonium (10 M), cytochalasin B (5 microg/ml), genistein (10 nM), herbimycin A (10 M) and Z-VAD-FMK (10 microM).


METHODS
Measurement of phosphatidylserine exposure and DNA fragmentation in flow cytometry and assessment of H2O2-production through spectrofluorometry. The results were analysed using Mann Whitney U test and Kruskal Wallis.


RESULTS
Pansorbins coated with antibodies to CD18 induce apoptosis in neutrophils (p<0.01), and activate the production of reactive oxygen species (p<0.01). Pre-treatment with the inhibitors have no effect on anti-CD 18 induced apoptosis.


CONCLUSIONS
Anti-CD18 pansorbins induce apoptosis in neutrophils through an alternative pathway not involving reactive oxygen species and independent of tyrosine phosphorylation, cytoskeletal reorganisation and caspases.
Larsson
J
J
Division of Pathology II, Faculty of Health Sciences, Linköping University, Sweden. jenny.larsson@inr.liu.se
Serrander
L
L
Stendahl
O
O
Lundqvist-Gustafsson
H
H
D000328:Adult; D017209:Apoptosis; D018821:CD18 Antigens / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis; D010766:Phosphorylation; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D018821:CD18 Antigens; D017382:Reactive Oxygen Species; D014443:Tyrosine