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Comparisons of CapG and gelsolin- macrophages: demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing.

Witke W, Li W, Kwiatkowski DJ, Southwick FS - J. Cell Biol. (2001)

Bottom Line: However, the loss of CapG in bone marrow macrophages profoundly inhibits macrophage colony stimulating factor-stimulated ruffling; reintroduction of CapG protein by microinjection fully restores this function.These motile functions are not impaired in gelsolin- macrophages and no additive effects are observed in CapG/gelsolin double- macrophages, establishing that CapG function is distinct from, and does not overlap with, gelsolin in macrophages.These primary effects on macrophage motile function suggest that CapG may be a useful target for the regulation of macrophage-mediated inflammatory responses.

View Article: PubMed Central - PubMed

Affiliation: Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.

ABSTRACT
Capping the barbed ends of actin filaments is a critical step for regulating actin-based motility in nonmuscle cells. The in vivo function of CapG, a calcium-sensitive barbed end capping protein and member of the gelsolin/villin family, has been assessed using a Capg allele engineered into mice. Both CapG- mice and CapG/gelsolin double- mice appear normal and have no gross functional abnormalities. However, the loss of CapG in bone marrow macrophages profoundly inhibits macrophage colony stimulating factor-stimulated ruffling; reintroduction of CapG protein by microinjection fully restores this function. CapG- macrophages also demonstrate approximately 50% impairment of immunoglobulin G, and complement-opsonized phagocytosis and lanthanum-induced vesicle rocketing. These motile functions are not impaired in gelsolin- macrophages and no additive effects are observed in CapG/gelsolin double- macrophages, establishing that CapG function is distinct from, and does not overlap with, gelsolin in macrophages. Our observations indicate that CapG is required for receptor-mediated ruffling, and that it is a major functional component of macrophage phagocytosis. These primary effects on macrophage motile function suggest that CapG may be a useful target for the regulation of macrophage-mediated inflammatory responses.

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Related in: MedlinePlus

Comparisons of wild-type, Gsn−/−, Capg−/−, and Gsn−/−/Capg−/− bone marrow macrophages. Removal of gelsolin failed to significantly impair any of the motile functions tested. (A) Bar graphs comparing the ruffling indexes of all four types of macrophages before and after exposure to MCSF. Brackets represent the SEM of n = 90–100 cells for each group. (B) Line graphs comparing the phagocytic rate for IgG-opsonized zymosan ingestion in the four cell types. Brackets represent the SEM of n = 90–100. (C) Bar graphs comparing the vesicle rocket velocities in the four cell types. Brackets represent the SEM of n = 90–100. C, Capg; G, Gsn.
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fig8: Comparisons of wild-type, Gsn−/−, Capg−/−, and Gsn−/−/Capg−/− bone marrow macrophages. Removal of gelsolin failed to significantly impair any of the motile functions tested. (A) Bar graphs comparing the ruffling indexes of all four types of macrophages before and after exposure to MCSF. Brackets represent the SEM of n = 90–100 cells for each group. (B) Line graphs comparing the phagocytic rate for IgG-opsonized zymosan ingestion in the four cell types. Brackets represent the SEM of n = 90–100. (C) Bar graphs comparing the vesicle rocket velocities in the four cell types. Brackets represent the SEM of n = 90–100. C, Capg; G, Gsn.

Mentions: In contrast to Capg−/− macrophages, Gsn−/− macrophages had somewhat increased spontaneous and CSF-induced ruffling activity compared with wild-type cells, although this difference did not achieve statistical significance. Double- Capg−/−Gsn−/− macrophages displayed spontaneous and MCSF-induced ruffling activity that was nearly identical to that of Capg−/− macrophages (Fig. 8 A).


Comparisons of CapG and gelsolin- macrophages: demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing.

Witke W, Li W, Kwiatkowski DJ, Southwick FS - J. Cell Biol. (2001)

Comparisons of wild-type, Gsn−/−, Capg−/−, and Gsn−/−/Capg−/− bone marrow macrophages. Removal of gelsolin failed to significantly impair any of the motile functions tested. (A) Bar graphs comparing the ruffling indexes of all four types of macrophages before and after exposure to MCSF. Brackets represent the SEM of n = 90–100 cells for each group. (B) Line graphs comparing the phagocytic rate for IgG-opsonized zymosan ingestion in the four cell types. Brackets represent the SEM of n = 90–100. (C) Bar graphs comparing the vesicle rocket velocities in the four cell types. Brackets represent the SEM of n = 90–100. C, Capg; G, Gsn.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196452&req=5

fig8: Comparisons of wild-type, Gsn−/−, Capg−/−, and Gsn−/−/Capg−/− bone marrow macrophages. Removal of gelsolin failed to significantly impair any of the motile functions tested. (A) Bar graphs comparing the ruffling indexes of all four types of macrophages before and after exposure to MCSF. Brackets represent the SEM of n = 90–100 cells for each group. (B) Line graphs comparing the phagocytic rate for IgG-opsonized zymosan ingestion in the four cell types. Brackets represent the SEM of n = 90–100. (C) Bar graphs comparing the vesicle rocket velocities in the four cell types. Brackets represent the SEM of n = 90–100. C, Capg; G, Gsn.
Mentions: In contrast to Capg−/− macrophages, Gsn−/− macrophages had somewhat increased spontaneous and CSF-induced ruffling activity compared with wild-type cells, although this difference did not achieve statistical significance. Double- Capg−/−Gsn−/− macrophages displayed spontaneous and MCSF-induced ruffling activity that was nearly identical to that of Capg−/− macrophages (Fig. 8 A).

Bottom Line: However, the loss of CapG in bone marrow macrophages profoundly inhibits macrophage colony stimulating factor-stimulated ruffling; reintroduction of CapG protein by microinjection fully restores this function.These motile functions are not impaired in gelsolin- macrophages and no additive effects are observed in CapG/gelsolin double- macrophages, establishing that CapG function is distinct from, and does not overlap with, gelsolin in macrophages.These primary effects on macrophage motile function suggest that CapG may be a useful target for the regulation of macrophage-mediated inflammatory responses.

View Article: PubMed Central - PubMed

Affiliation: Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.

ABSTRACT
Capping the barbed ends of actin filaments is a critical step for regulating actin-based motility in nonmuscle cells. The in vivo function of CapG, a calcium-sensitive barbed end capping protein and member of the gelsolin/villin family, has been assessed using a Capg allele engineered into mice. Both CapG- mice and CapG/gelsolin double- mice appear normal and have no gross functional abnormalities. However, the loss of CapG in bone marrow macrophages profoundly inhibits macrophage colony stimulating factor-stimulated ruffling; reintroduction of CapG protein by microinjection fully restores this function. CapG- macrophages also demonstrate approximately 50% impairment of immunoglobulin G, and complement-opsonized phagocytosis and lanthanum-induced vesicle rocketing. These motile functions are not impaired in gelsolin- macrophages and no additive effects are observed in CapG/gelsolin double- macrophages, establishing that CapG function is distinct from, and does not overlap with, gelsolin in macrophages. Our observations indicate that CapG is required for receptor-mediated ruffling, and that it is a major functional component of macrophage phagocytosis. These primary effects on macrophage motile function suggest that CapG may be a useful target for the regulation of macrophage-mediated inflammatory responses.

Show MeSH
Related in: MedlinePlus