ISSN:
1600-0765
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Peripheral neutrophils from patients with localized juvenile periodontitis (LJP) show functional abnormalities, such as impaired locomotion and enhanced respiratory burst activity. A defect in intracellular signalling mechanism has been proposed to be responsible for some changes, but direct evidence is lacking. In this study we have determined the activity of diacylglycerol (DAG) kinase, an enzyme controlling the DAG/protein kinase C (PKC)-pathway, in crude cytosolic and membrane fractions of neutrophils from 5 LJP patients and age and gender-matched normal individuals. No difference was observed in the DAG kinase activity in subcellular fractions from unstimulated cells between the 2 groups. When normal neutrophils were stimulated with N–formyl–methionyl-leucyl-phenylalanine (FMLP), the enzyme activity was markedly increased in both subcellular fractions. In contrast, neutrophils from 3 of the 5 LJP patients tested completely failed to rise the DAG kinase activity upon chemoattractant stimulation. These data indicate that in some LJP patients the neutrophil DAG kinase may be defective. To examine whether a decrease in DAG kinase activity could account for some neutrophil abnormalities seen in LJP, normal neutrophils were treated with R59O22, a DAG kinase inhibitor, that has been shown to reduce DAG kinase activity in human neutrophils. Upon stimulation with FMLP, R59O22-treated normal neutrophils showed significantly reduced chemotactic response and enhanced respiratory burst activity, two typical functional abnormalities featured by LJP cells. It is concluded that a defect in DAG kinase may cause, through an abnormal accumulation of the endogenous PKC activator DAG, some of the functional changes observed in neutrophils from LJP patients.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1600-0765.1997.tb00550.x
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