Differential localization of protein kinase C isotypes in equine eosinophils and neutrophils.
Abstract: Phorbol esters, which activate protein kinase C (PKC), stimulate equine eosinophil superoxide production and adherence. After showing that superoxide production could be inhibited by the nonselective PKC inhibitors, staurosporine and bisindolymaleimide I, the PKC isotypes in equine eosinophils were characterized, because evidence suggests that individual isotypes may play distinct roles in regulating eosinophil function. Western blots demonstrated that equine eosinophils expressed PKC alpha, beta, delta, epsilon, iota, and zeta. However, unlike the equine neutrophil, the majority of the PKC was detected in the particulate fraction of the cell. Despite this unusual location, the PKC in equine eosinophils was activatable, suggesting that it is functionally competent. The regulatory role of PKC in equine eosinophils may reflect the association of activity with the particulate fraction and the profile of isotype expression.
Publication Date: 2000-10-19 PubMed ID: 11037981
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research reveals that different isotypes of protein kinase C (PKC), a key protein involved in immune cell function, are found in variable locations within certain dog immune cells known as eosinophils and neutrophils, influencing their responses to infections and inflammations.
Introduction and Objectives
- The study is primarily focused on the position and function of protein kinase C (PKC), a vital protein in managing the functions of immune cells, which are eosinophils and neutrophils in horses.
- It investigates whether different versions (isotypes) of PKC are found in different areas within these vital cells, and how these variations might influence the cells’ responses to infections and inflammation.
Methods and Findings
- The researchers used compounds called phorbol esters to activate the Protein kinase C (PKC) in eosinophils, which resulted in enhanced superoxide production and adherence, processes vital for the cells’ functions in fighting infections.
- The study showed that when PKC was blocked with nonselective inhibitors, superoxide production was inhibited. This indicates that PKC has a crucial role in eosinophil function.
- Further exploratory work identified specific isotypes of PKC present in horse eosinophils, namely PKC alpha, beta, delta, epsilon, iota, and zeta.
- An interesting finding was that, unlike in neutrophils, where PKC is widely distributed within the cell, most of the PKC in eosinophils was found in the ‘particulate fraction’ of the cell – essentially the more solid parts rather than the fluid parts.
- Despite this unusual positioning, the PKC in the eosinophils was still able to be activated and presumably carry out its normal functions, suggesting that it is functionally effective regardless of its location.
Conclusions and Implications
- The research concludes that the unique activity of PKC in eosinophils could be due to its close association with the particulate fraction of the cell and the specific profile of isotype expression.
- This study adds to our understanding of the complexity of immune response regulation and may have implications for the study and treatment of immune-related diseases in veterinary medicine.
Cite This Article
APA
Greenaway EC, Cunningham FM, Goode NT.
(2000).
Differential localization of protein kinase C isotypes in equine eosinophils and neutrophils.
J Leukoc Biol, 68(4), 575-582.
Publication
Researcher Affiliations
- Department of Veterinary Basic Sciences, The Royal Veterinary College, London, UK.
MeSH Terms
- Animals
- Brain / enzymology
- Cell Membrane / enzymology
- Cell Nucleus / enzymology
- Cytoplasmic Granules / enzymology
- Enzyme Activation / drug effects
- Enzyme Inhibitors / pharmacology
- Eosinophils / drug effects
- Eosinophils / enzymology
- Horses / blood
- Indoles / pharmacology
- Intracellular Membranes / enzymology
- Isoenzymes / antagonists & inhibitors
- Isoenzymes / blood
- Maleimides / pharmacology
- Neutrophils / drug effects
- Neutrophils / enzymology
- Organ Specificity
- Protein Kinase C / antagonists & inhibitors
- Protein Kinase C / blood
- Rats
- Respiratory Burst / drug effects
- Staurosporine / pharmacology
- Subcellular Fractions / enzymology
- Superoxides / blood
- Tetradecanoylphorbol Acetate / pharmacology
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