Superoxide production at phagosomal cup/phagosome through βI protein kinase C during FcγR-mediated phagocytosis in microglia

Takehiko Ueyama, Michelle E. Lennartz, Yukiko Noda, Toshihiro Kobayashi, Yasuhito Shirai, Kyoko Rikitake, Tomoko Yamasaki, Shigeto Hayashi, Norio Sakai, Harumichi Seguchi, Makoto Sawada, Hideki Sumimoto, Naoaki Saito

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Protein kinase C (PKC) plays a prominent role in immune signaling. To elucidate the signal transduction in a respiratory burst and isoform-specific function of PKC during FcγR-mediated phagocytosis, we used live, digital fluorescence imaging of mouse microglial cells expressing GFP-tagged molecules. βI PKC, εPKC, and diacylglycerol kinase (DGK) β dynamically and transiently accumulated around IgG-opsonized beads (BIgG). Moreover, the accumulation of p47phox, an essential cytosolic component of NADPH oxidase and a substrate for βI PKC, at the phagosomal cup/phagosome was apparent during BIgG ingestion. Superoxide (O2-) production was profoundly inhibited by Gö6976, a cPKC inhibitor, and dramatically increased by the DGK inhibitor, R59949. UItrastractural analysis revealed that BIgG induced O2- production at the phagosome but not at the intracellular granules. We conclude that activation/accumulation of βI PKC is involved in O2- production, and that O2- production is primarily initiated at the phagosomal cup/phagosome. This study also suggests that DGKβ plays a prominent role in regulation of O2- production during FcγR-mediated phagocytosis.

Original languageEnglish
Pages (from-to)4582-4589
Number of pages8
JournalJournal of Immunology
Volume173
Issue number7
Publication statusPublished - Oct 1 2004

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Phagosomes
Microglia
Phagocytosis
Superoxides
Protein Kinase C
Diacylglycerol Kinase
R 59949
Respiratory Burst
NADPH Oxidase
Optical Imaging
Signal Transduction
Protein Isoforms
Eating
Immunoglobulin G

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ueyama, T., Lennartz, M. E., Noda, Y., Kobayashi, T., Shirai, Y., Rikitake, K., ... Saito, N. (2004). Superoxide production at phagosomal cup/phagosome through βI protein kinase C during FcγR-mediated phagocytosis in microglia. Journal of Immunology, 173(7), 4582-4589.

Superoxide production at phagosomal cup/phagosome through βI protein kinase C during FcγR-mediated phagocytosis in microglia. / Ueyama, Takehiko; Lennartz, Michelle E.; Noda, Yukiko; Kobayashi, Toshihiro; Shirai, Yasuhito; Rikitake, Kyoko; Yamasaki, Tomoko; Hayashi, Shigeto; Sakai, Norio; Seguchi, Harumichi; Sawada, Makoto; Sumimoto, Hideki; Saito, Naoaki.

In: Journal of Immunology, Vol. 173, No. 7, 01.10.2004, p. 4582-4589.

Research output: Contribution to journalArticle

Ueyama, T, Lennartz, ME, Noda, Y, Kobayashi, T, Shirai, Y, Rikitake, K, Yamasaki, T, Hayashi, S, Sakai, N, Seguchi, H, Sawada, M, Sumimoto, H & Saito, N 2004, 'Superoxide production at phagosomal cup/phagosome through βI protein kinase C during FcγR-mediated phagocytosis in microglia', Journal of Immunology, vol. 173, no. 7, pp. 4582-4589.
Ueyama T, Lennartz ME, Noda Y, Kobayashi T, Shirai Y, Rikitake K et al. Superoxide production at phagosomal cup/phagosome through βI protein kinase C during FcγR-mediated phagocytosis in microglia. Journal of Immunology. 2004 Oct 1;173(7):4582-4589.
Ueyama, Takehiko ; Lennartz, Michelle E. ; Noda, Yukiko ; Kobayashi, Toshihiro ; Shirai, Yasuhito ; Rikitake, Kyoko ; Yamasaki, Tomoko ; Hayashi, Shigeto ; Sakai, Norio ; Seguchi, Harumichi ; Sawada, Makoto ; Sumimoto, Hideki ; Saito, Naoaki. / Superoxide production at phagosomal cup/phagosome through βI protein kinase C during FcγR-mediated phagocytosis in microglia. In: Journal of Immunology. 2004 ; Vol. 173, No. 7. pp. 4582-4589.
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