Insulin inhibits phagocytosis in normal human neutrophils via PKCalpha/beta-dependent priming of F-actin assembly.
2006 (English)In: Inflammation Research, ISSN 1023-3830, Vol. 55, no 3, 85-91 p.Article in journal (Refereed) Published
OBJECTIVE: This study investigated the effects of insulin on the phagocytosis of C3bi - and IgG-opsonized yeast particles in normal human neutrophils. METHODS: Neutrophils were incubated in different insulin concentrations for 30 minutes and stimulated by C3bi - or IgG-opsonized yeast particles. Phagocytosis was quantified by both light microscopy and FACscan flow cytometry. Laser confocal microscopy was used for quantification of F-actin levels. RESULTS: Elevated insulin concentrations decreased neutrophil phagocytosis of both types of targets. This defect was shown to be in part due to a delayed phagocytosis in the presence of insulin. Following a 30 minute incubation, insulin was found to increase the accumulation of cortical F-actin, without affecting the total cellular F-actin content. The specific PKCalpha/beta inhibitor, Go6976, abolished the insulin-mediated increase in cortical F-actin content and both Go6976 and the PKCalpha/beta/delta/epsilon-specific inhibitor GF109203X reversed the inhibitory effects of insulin on phagocytosis. CONCLUSION: Hyperinsulinemia in vitro can inhibit phagocytosis of opsonized targets in normal human neutrophils. This effect of insulin is dependent on activation of PKCalpha and/or PKCbeta, and these insulin signals may interfere with the dynamic assembly/disassembly and/or distribution of F-actin, which is required for the phagocytosis process.
Place, publisher, year, edition, pages
2006. Vol. 55, no 3, 85-91 p.
IdentifiersURN: urn:nbn:se:umu:diva-12283DOI: doi:10.1007/s00011-005-0009-1PubMedID: 16673150OAI: oai:DiVA.org:umu-12283DiVA: diva2:151954