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Selective inhibition of IgG-mediated phagocytosis in gelsolin-deficient murine neutrophils

Skarman, P.
Rasmussen, B.
Witke, W.
Stendahl, O.
Published in The Journal of immunology. 2000, vol. 165, no. 5, p. 2451-2457
Abstract Phagocytosis and the microbicidal functions of neutrophils require dynamic changes of the actin cytoskeleton. We have investigated the role of gelsolin, a calcium-dependent actin severing and capping protein, in peripheral blood neutrophils from gelsolin-null (Gsn-) mice. The phagocytosis of complement opsonized yeast was only minimally affected. In contrast, phagocytosis of IgG-opsonized yeast was reduced close to background level in Gsn- neutrophils. Thus, gelsolin is essential for efficient IgG- but not complement-mediated phagocytosis. Furthermore, attachment of IgG-opsonized yeast to Gsn- neutrophils was reduced ( approximately 50%) but not to the same extent as ingestion ( approximately 73%). This was not due to reduced surface expression of the Fcgamma-receptor or its lateral mobility. This suggests that attachment and ingestion of IgG-opsonized yeast by murine neutrophils are actin-dependent and gelsolin is important for both steps in phagocytosis. We also investigated granule exocytosis and several steps in phagosome processing, namely the formation of actin around the phagosome, translocation of granules, and activation of the NADPH-oxidase. All these functions were normal in Gsn- neutrophils. Thus, the role of gelsolin is specific for IgG-mediated phagocytosis. Our data suggest that gelsolin is part of the molecular machinery that distinguishes complement and IgG-mediated phagocytosis. The latter requires a more dynamic reorganization of the cytoskeleton.
Keywords Actins/metabolismAnimalsBinding Sites/immunologyBiological Transport/immunologyCalcium/physiologyCell Membrane/immunology/metabolismCytoplasmic Granules/metabolismGelsolin/ deficiency/ genetics/physiologyGuanosine 5'-O-(3-Thiotriphosphate)/physiologyImmune Tolerance/ geneticsImmunoglobulin G/metabolism/ physiologyMiceMice, Inbred C57BLMice, TransgenicNeutrophils/ immunology/ metabolism/secretionNitroblue Tetrazolium/metabolismOpsonin Proteins/metabolismOxidation-ReductionPhagocytosis/ geneticsPhagosomes/metabolismReceptors, Complement/biosynthesis/metabolism/physiologyReceptors, IgG/biosynthesis/metabolism/physiology
PMID: 10946270
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Other version: http://www.jimmunol.org/cgi/reprint/165/5/2451.pdf
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SERRANDER, Lena et al. Selective inhibition of IgG-mediated phagocytosis in gelsolin-deficient murine neutrophils. In: The Journal of immunology, 2000, vol. 165, n° 5, p. 2451-2457. doi: 10.4049/jimmunol.165.5.2451 https://archive-ouverte.unige.ch/unige:7582

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Deposited on : 2010-06-21

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