Protein Kinase C-α Participates in FcγR-Mediated Phagocytosis in Macrophages

Breton, Anouk; Descoteaux, Albert

doi:10.1006/bbrc.2000.3511

Cited by 50 publications

(29 citation statements)

References 33 publications

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“…However, it is possible that PKCα is inhibited by the PKCβ peptide inhibitor. Therefore, whether PKCα, which has also been implicated in cell IgG-mediated phagocytosis (Breton 2000, Larson 2000, cell spreading, migration, integrin signaling (Larsson 2006), and calcium signaling (Reither 2006), participates in the events outlined in Figure 9 remains unclear. Alternatively, PKCα may play post-fusion roles in as yet undescribed FBGC activities at sites of chronic inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…These include PKCα in Fcγ receptormediated phagocytosis (Breton 2000) and in the IgG-stimulated respiratory burst (Larsen 2000), PKCβ in the phagocytosis of latex particles (Dieter 2000), and PKCβ and PKCδ in the phagocytosis of L. monocytogenes and translocation of PKCβ to early endosomes during bacterial escape from phagocytic vesicles (Wadsworth 2002). Novel PKCs δ and ε have also been linked to IgG-stimulated phagocytosis (Larsen 2000), and the phagocytosis of apoptotic cells by monocytes/macrophages requires PKC activity (Liu 2005).…”

Section: Introductionmentioning

confidence: 99%

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Foreign body-type multinucleated giant cell formation requires protein kinase C β, δ, and ζ

McNally

MacEwan

Anderson

2008

Experimental and Molecular Pathology

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Multinucleated giant cells are a classic cellular feature of chronic inflammation, although the mechanism of macrophage fusion leading to their formation is not well understood. Here, we investigate the participation of protein kinase C (PKC) in the interleukin (IL)-4-induced fusion of human monocyte-derived macrophages and foreign body giant cell (FBGC) formation in vitro. The PKC inhibitors H-7 and calphostin C attenuated macrophage fusion, whereas H-8, which is more selective for PKA and PKG, did not. Macrophage fusion was also prevented by the phospholipase C inhibitor, Et-18-OCH 3 , the PKC isoform inhibitors GO6983 or rottlerin and by peptide inhibitors for PKC (20-28), PKCβ, or PKCζ but not by HBDDE or peptide inhibitors for PKCε or PKA. In cultures of fusing macrophages/FBGC, we detected only PKCα, β, δ, and ζ by immunoprecipitation and immunoblotting, and we also observed strong expression of these isoforms by immunocytochemistry. Our collective results suggest that the γ, ε, η, μ, θ, or ι PKC isoforms are not required in the mechanism of IL-4-induced macrophage fusion; whether PKCα is required is unclear. However, new evidence is provided that FBGC formation is supported by PKCβ, PKCδ, and PKCζ in combined diacylglycerol-dependent (PKCβ and PKCδ) and -independent (PKCζ) signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Foreign body-type multinucleated giant cell formation requires protein kinase C β, δ, and ζ

McNally

MacEwan

Anderson

2008

Experimental and Molecular Pathology

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“…Among these signal transduction pathway components, Src family kinases, Syk kinase and the adapter protein LAT have all been shown to play critical roles in Fc␥R-regulated phagocytosis (75,(77)(78)(79). In addition, FcR-mediated phagocytosis is via Ca 2ϩ -dependent and Ca 2ϩ -independent pathways (80 -83) Moreover, PKC, which is activated by PLC␥, has been reported to play a role in regulating phagocytosis (83,84). It was surprising, therefore, that PLC␥2-deficient macrophages phagocytosed IgG2a (Fc␥RI-dependent) or IgG2b (Fc␥RII/ III-dependent) immune complexes normally compared with wildtype macrophages, especially in light of the observation that these mutant macrophages did not express the alternative PLC␥1 isoform and failed to mobilize Ca 2ϩ in response to Fc␥R cross-linking.…”

Section: Discussionmentioning

confidence: 99%

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

Wen

Jou

Chen

et al. 2002

The Journal of Immunology

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Phospholipase Cγ2 (PLCγ2) plays a critical role in the functions of the B cell receptor in B cells and of the FcRγ chain-containing collagen receptor in platelets. Here we report that PLCγ2 is also expressed in mast cells and monocytes/macrophages and is activated by cross-linking of FcεR and FcγR. Although PLCγ2-deficient mice have normal development and numbers of mast cells and monocytes/macrophages, we demonstrate that PLCγ2 is essential for specific functions of FcεR and FcγR. While PLCγ2-deficient mast cells have normal mitogen-activated protein kinase activation and cytokine production at mRNA levels, the mutant cells have impaired FcεR-mediated Ca2+ flux and inositol 1,4,5-trisphosphate production, degranulation, and cytokine secretion. As a physiological consequence of the effect of PLCγ2 deficiency, the mutant mice are resistant to IgE-mediated cutaneous inflammatory skin reaction. Macrophages from PLCγ2-deficient mice have no detectable FcγR-mediated Ca2+ flux; however, the mutant cells have normal FcγR-mediated phagocytosis. Moreover, PLCγ2 plays a nonredundant role in FcγR-mediated inflammatory skin reaction.

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“…However, because PKC co-localization may be a consequence rather than a necessary process, other groups have investigated blockade of PKC function. Overexpression of a dominant negative mutant of PKC ␣ in the murine Mø cell line RAW 264.7 reduced phagocytosis of IgG-opsonized sheep red blood cells (54) but not phagocytosis of Leishmania donovani promastigotes (55). Although the former finding was interpreted to indicate a requirement for PKC ␣ in Fc␥R-mediated phagocytosis, such observations must be interpreted with caution, because overexpression of one PKC isozyme can alter the levels of other PKC isoforms (56).…”

Section: Discussionmentioning

confidence: 99%

Activation of Protein Kinase C βII by the Stereo-specific Phosphatidylserine Receptor Is Required for Phagocytosis of Apoptotic Thymocytes by Resident Murine Tissue Macrophages

Todt¹,

Hu²,

Punturieri³

et al. 2002

Journal of Biological Chemistry

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We showed previously that protein kinase C (PKC) is required for phagocytosis of apoptotic leukocytes by murine alveolar (AMø) and peritoneal macrophages (PMø) and that such phagocytosis is markedly lower in AMø compared with PMø. In this study, we examined the roles of individual PKC isoforms in phagocytosis of apoptotic thymocytes by these two Mø populations. By immunoblotting, AMø expressed equivalent PKC but lower amounts of other isoforms (␣, ␤I, ␤II, ␦, ⑀, , and ), with the greatest difference in ␤II expression. A requirement for PKC ␤II for phagocytosis was demonstrated collectively by phorbol 12-myristate 13-acetate-induced depletion of PKC ␤II, by dose-response to PKC inhibitor Ro-32-0432, and by use of PKC ␤II myristoylated peptide as a blocker. Exposure of PMø to phosphatidylserine (PS) liposomes specifically induced translocation of PKC ␤II and other isoforms to membranes and cytoskeleton. Both AMø and PMø expressed functional PS receptor, blockade of which inhibited PKC ␤II translocation. Our results indicate that murine tissue Mø require PKC ␤II for phagocytosis of apoptotic cells, which differs from the PKC isoform requirement previously described in Mø phagocytosis of other particles, and imply that a crucial action of the PS receptor in this process is PKC ␤II activation.

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Protein Kinase C-α Participates in FcγR-Mediated Phagocytosis in Macrophages

Cited by 50 publications

References 33 publications

Foreign body-type multinucleated giant cell formation requires protein kinase C β, δ, and ζ

Foreign body-type multinucleated giant cell formation requires protein kinase C β, δ, and ζ

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

Activation of Protein Kinase C βII by the Stereo-specific Phosphatidylserine Receptor Is Required for Phagocytosis of Apoptotic Thymocytes by Resident Murine Tissue Macrophages

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