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Cited by 118Phagocytosis and Immune RegulationProtein Kinase Regulation and GTPase SignalingCellular transport and secretion

Immunoglobulin-mediated phagocytosis by human monocytes requires protein kinase C activation. Evidence for protein kinase C translocation to phagosomes

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Zheleznyak, A, Brown, E.J.·1992·Journal of Biological Chemistry
DOI 10.1016/s0021-9258(19)49803-7
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Abstract

This study has investigated the role of protein kinase C (PKC) activation in IgG-mediated phagocytosis by human monocytes. Incubation of monocytes with IgG-opsonized targets increased membrane-associated PKC approximately 2-fold. Kinetic studies showed that the translocation of PKC to membrane occurred before significant ingestion took place. The pharmacologic PKC inhibitor H7 inhibited IgG-dependent ingestion with ID50 of 20 microM, while the structurally related isoquinoline sulfonamide HA1004 had no effect at this concentration. Staurosporine and calphostin C, PKC inhibitors which have different mechanisms of actions than H7, also inhibited ingestion. Depletion of PKC by prolonged incubation with phorbol esters also inhibited phagocytosis, and dose-response curves showed a strong correlation between the extent of PKC depletion and the extent of inhibition of ingestion. Finally, phagosomes were isolated by sucrose density centrifugation of cells disrupted 5 min after the initiation of phagocytosis. Measurement of PKC activity and immunoreactivity in the phagosomes showed that PKC was concentrated in the phagosome membrane approximately 5-fold compared to the uninvolved plasma membrane. Together, these data suggest that PKC activation is an early, essential step in the efficient ingestion of IgG-opsonized targets by monocytes.

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Crossref · 10.1016/s0021-9258(19)49803-7

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  • Both PKCα and PKCδ copurify with isolated phagosomal membranes, and some inhibitors of PKC activity have been reported to interfere with phagocytosis.

    “both PKCα and PKCδ copurify with isolated phagosomal membranes (Allen and Aderem 1995; Brumell et al. 1999) and some inhibitors of PKC activity have been reported to interfere with phagocytosis (Zheleznyak and Brown 1992; Karimi et al. 1999).”

    From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Zheleznyak and Brown 1992

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Authors
Zheleznyak, A., & Brown, E. J.
Affiliations
Washington University in St. Louis (US)
ORCID
Brown, E.J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1992-06
Volume
267
Issue
17
Pages
12042-12048
ISSN
0021-9258 (ISSN-L)
DOI
10.1016/s0021-9258(19)49803-7
OpenAlex
W1567522204
Cited by
118
References
27
Citations by year
2024: 4 · 2022: 1 · 2021: 3 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 1
FWCI
2.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (GM38330, R01GM038330)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
protein kinase C, phagocytosis, monocytes, IgG opsonization, phagosome, PKC translocation, PKC inhibitors, H7, staurosporine, calphostin C, phorbol ester
MeSH terms
Alkaline Phosphatase, Alkaloids, Amino Acid Sequence, Biological Transport, Electrophoresis, Polyacrylamide Gel, Enzyme Activation, Eye Proteins, Humans, Immunoglobulin G, Isoquinolines, Kinetics, Molecular Sequence Data, Monocytes, Naphthalenes, Phagocytosis, Phagosomes, Piperazines, Polycyclic Compounds, Protein Kinase C, Sulfonamides, Blotting, Western, Signal Transduction, Rod Opsins, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Staurosporine

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