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Veterinary immunology and immunopathology2003; 96(1-2); 53-63; doi: 10.1016/s0165-2427(03)00161-2

Protein kinase C (PKC) isotype profile in eosinophils from ponies with sweet itch and role in histamine-induced eosinophil activation.

Abstract: Eosinophils have been implicated in the pathogenesis of the seasonal equine allergic skin disease, sweet itch. Protein kinase C (PKC) is involved in regulating eosinophil function and antigen challenge has been reported to alter PKC isotype expression in blood eosinophils from allergic human subjects. Here we have compared the pattern of PKC isotype expression in eosinophils from sweet itch ponies with that in cells from normal ponies both during the active and inactive phases of the disease. A role for PKC in histamine-induced eosinophil activation was also investigated. Conventional PKCs alpha and beta, novel PKCs delta and epsilon and atypical PKCs iota and zeta were identified in eosinophils pooled from four allergic ponies during the inactive phase, when no clinical signs were evident. The PKC isotypes, like those in eosinophils from normal ponies, were located primarily in the particulate fraction of the cell. Isotype expression in cells from normal and allergic animals did not appear to be different. In contrast, during the active phase of the disease, when the sweet itch ponies had clinical signs, the expression of PKCs beta, epsilon and iota in eosinophils from these animals appeared to be increased relative to that in cells from normal ponies. When PKC expression in eosinophils from five individual normal and sweet itch ponies was compared, small, but statistically significant, increases in PKC epsilon and PKCdelta expression were evident in eosinophils from the sweet itch ponies during the active and inactive phases, respectively. The non-selective PKC inhibitors, staurosporine and Ro31-8220, significantly reduced histamine-induced superoxide production. Use of Gö6976, an inhibitor of conventional PKCs, suggested that PKCalpha and/or beta were involved and that there was significantly greater inhibition of the response in eosinophils obtained from sweet itch ponies during the active phase. There was no significant difference in histamine-induced superoxide production by eosinophils from allergic and normal ponies and the functional significance of the increased PKC isotype expression in eosinophils from sweet itch ponies relative to that in cells from healthy animals remains to be established.
Publication Date: 2003-10-03 PubMed ID: 14522134DOI: 10.1016/s0165-2427(03)00161-2Google Scholar: Lookup
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  • Journal Article
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Summary

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This research investigates the role of protein kinase C (PKC) in histamine-induced eosinophil activation in ponies with a seasonal allergic skin disease called sweet itch. The study compares the PKC isotype patterns in these animals to healthy ponies during both active and inactive disease phases, and identifies variations in PKC isotype expressions which could enhance our understanding of the disease’s pathogenesis.

Understanding the Role of Protein Kinase C (PKC) in Eosinophil Activation

Eosinophils, a type of white blood cell, have a key role in allergic reactions. They are implicated in the seasonal equine skin disease known as sweet itch. This study discusses the following findings:

  • The role of Protein Kinase C (PKC) in controlling eosinophil functionality.
  • The variations in the expression of PKC isotypes in blood eosinophils from allergic individuals following an antigen challenge.

Pattern of PKC Isotype Expression in Eosinophils from Ponies with Sweet Itch

The study reveals several important points on this subject:

  • The researchers compared the PKC isotype expressions in eosinophils from ponies with sweet itch against normal ponies, in active and inactive disease phases.
  • The eosinophils expressed several PKC isotypes (alpha, beta, delta, epsilon, iota, and zeta). These isotypes were primarily located in the particulate fraction of the cell.
  • During the disease’s active phase, there were observable increases in the expression of beta, epsilon and iota PKCs in eosinophils from affected animals. This contrasted with the expression in cells from healthy ponies.

Role of PKC in Histamine-induced Eosinophil Activation

Insights on how PKC may be involved in histamine-driven eosinophil activation were revealed in the study:

  • When PKC expression was compared in eosinophils from normal and sweet itch-affected ponies, small yet significant gains in the expression of PKC epsilon and PKC delta were noted in the affected ponies during active and inactive periods, respectively.
  • The non-selective PKC inhibitors, such as staurosporine and Ro31-8220, markedly decreased histamine-induced superoxide production, suggesting that PKC plays a significant role in this process.
  • The use of Gö6976, an inhibitor of conventional PKCs, indicated that PKCalpha and/or PKCbeta were implicated. Moreover, the response was significantly lower in eosinophils from ponies with active sweet itch.
  • There was no noteworthy variation between eosinophils from normal and affected ponies in terms of histamine-induced superoxide production. The exact functional significance of enhanced PKC isotype expression in eosinophils from sweet itch-affected ponies, in comparison to healthy ones, remains unclear and warrant further investigation.

Cite This Article

APA
Greenaway EC, Sepulveda MF, Cunningham FM, Goode NT. (2003). Protein kinase C (PKC) isotype profile in eosinophils from ponies with sweet itch and role in histamine-induced eosinophil activation. Vet Immunol Immunopathol, 96(1-2), 53-63. https://doi.org/10.1016/s0165-2427(03)00161-2

Publication

ISSN: 0165-2427
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 96
Issue: 1-2
Pages: 53-63

Researcher Affiliations

Greenaway, E C
  • Department of Veterinary Basic Sciences, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, UK.
Sepulveda, M F
    Cunningham, F M
      Goode, N T

        MeSH Terms

        • Animals
        • Blotting, Western / veterinary
        • Carbazoles / pharmacology
        • Dermatitis, Allergic Contact / enzymology
        • Dermatitis, Allergic Contact / immunology
        • Dermatitis, Allergic Contact / veterinary
        • Enzyme Inhibitors / pharmacology
        • Eosinophils / enzymology
        • Eosinophils / immunology
        • Histamine / immunology
        • Horse Diseases / enzymology
        • Horse Diseases / immunology
        • Horses
        • Indoles / pharmacology
        • Isoenzymes / antagonists & inhibitors
        • Isoenzymes / immunology
        • Lymphocyte Activation
        • Male
        • Protein Kinase C / antagonists & inhibitors
        • Protein Kinase C / immunology
        • Staurosporine / pharmacology
        • Superoxides / immunology
        • Superoxides / metabolism

        Citations

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